02

Respiratory System 04

Respiration

Respiration is the process by which an organism

Oxygen
takes in oxygen (inhalation) and releases carbon in
dioxide (exhalation). This oxygen is transported to
Carbon
all the cells in the body, which use it to produce Dioxide
energy from digested food. out

Respiratory System
The human respiratory system is a series of organs
responsible for taking in oxygen and expelling
carbon dioxide. The primary organs of the
respiratory system are lungs, which carry out this
exchange of gases as we breathe.
Module 1 | Respiratory and Nervous System
Structure of the Respiratory System 05
Bronchi
Nasal Cavity Two tubes inside of lungs
Passes air that air passes through
through nose to the bronchioles.
The upper respiratory system

The lower respiratory system

Pharynx Lungs
Cone shaped passageway Main organ of the
leading to trachea. respiratory system.

Larynx Bronchioles
Upper part of respiratory Small branching out
system, which contains tubes divided into
the vocal cords alveoli.
Alveoli
Trachea
Main tube Tiny air sacs where exchange of
connecting nose/mouth O2 and CO2 takes place
to lungs.
Diaphragm
A dome-shaped
muscle that separates
the lungs from the
Module 1 | Respiratory and Nervous System abdomen
 Gaseous Exchange 06

Gaseous Exchange is performed automatically by

the respiratory system. How it works: 1 Oxygen
1. The air, containing oxygen and other gases,
comes into the body through the lungs.
2 Pulmonary venule 3 Pulmonary
Carries
arteriole

Carries oxygenated deoxygenated

2. In the lungs, gaseous exchange takes place, the blood from the lung to the blood from the heart
oxygen is moved into the bloodstream heart
Bronchus
to the lungs

(oxygenated blood) and carried through the body.

Bronchiole

3. Red blood cells collect the carbon dioxide

(deoxygenated blood) and transport it back to the
lungs, where it leaves the body when we exhale. Capillaries

Alveoli
The exchange of oxygen and carbon
dioxide occurs in the alveoli

Module 1 | Respiratory and Nervous System

Gaseous Exchange (Cont.) 07

Module 1 | Respiratory and Nervous System

Functions of the Respiratory System 08

Coughing Respiration Olfaction

Reflex
action The action Sense of
of breathing smell

Module 1 | Respiratory and Nervous System

 Functions of the Respiratory System (Cont.) 09

Vocalization Thermoregulation Regulation of blood pH

To produce musical sounds with Exchange of gases (CO2 & O2)

Moistens the air we
the voice via vocal cords (larynx) maintains and stabilizes the normal
breathe to equilibrate
blood pH by liberation of acidic gas
with the temperature
(CO2).
of blood in the
capillaries.

Module 1 | Respiratory and Nervous System

 Fast Facts 10

Module 1 | Respiratory and Nervous System

 Nervous System 11
The nervous system is the system Central Nervous System Peripheral Nervous System
that processes and coordinates all
information by receiving and
Brain Cranial Nerves
transmitting signals to and from
different parts of the body.
Spinal Cord Spinal Nerves
It is made up of specialized cells called
neurons.
Sensory Organs
(eyes, nose, tongue,
Main functions: ears, and skin)
● It controls all the actions of our
body
● It sends and receives signals
from all parts of the body and
responds to changes
 Nervous System 12

A neuron is a nerve cell that is the basic building block of the nervous system. They are specialized to transmit information
throughout the body. These highly specialized nerve cells are responsible for communicating information in both chemical and
electrical forms.

Afferent neurons are sensory neurons that carry nerve impulses from effector cells towards the central nervous system.

Efferent neurons are motor neurons that carry neural impulses away from the central nervous system to the effector cells.

Module 1 | Respiratory and Nervous System

 Nervous System 13

Chemical substance (aka chemical messenger) released by synaptic terminals for the purpose of transmitting information from one
neuron to another.

Nerves are bundles of neurons that transmit sensory and motor information between the brain and spinal cord and the rest of the
body.

A nerve impulse is an electrical signal that travels along the axon.

Module 1 | Respiratory and Nervous System

Neuron and Neurotransmission 14
A small gap called the synaptic cleft
Cell body separates the transmitting & receiving
Dendrites neurons.

Neurotransmitters are
stored in the axon terminal.

Axon

The transmitting neuron

releases neurotransmitters
into the synaptic cleft.

Neurotransmitters bind to the

receptors in the plasma membrane of
Module 1 | Respiratory and Nervous System the receiving cell.
 The Nervous System 15
The Nervous System

Central NS Peripheral NS
(The body’s master control unit) (Consists of nerves and ganglia outside the
brain and spinal cord)

Spinal Cord Brain The Autonomic NS The Somatic NS

A column of Central Controls involuntary Carries sensory
nerves organ, bodily processes, information from
between the consists of including heart rate, sensory organs to the
brain and cerebrum, respiration, digestion CNS and relays motor
peripheral brainstem and pupil contraction; (movement) commands
nervous and operates automatically to the muscles; controls
system cerebellum. without conscious voluntary movements.
direction

Module 1 | Respiratory and Nervous System
Sympathetic NS
Prepares the body for actions and
stress. This is called ‘fight’ or ‘flight’
response
Neurotransmitters are epinephrine
and norepinephrine.
Parasympathetic NS
Conserves energy, non-immediate
response ‘rest & digest’.
Neurotransmitter is acetylcholine
(Ach)-‘Cholinergic’
Sympathetic vs Parasympathetic Nervous System 16

Parasympathetic Sympathetic
(Body at rest) (Emergency situations)

Constricts pupils Dilates pupils

Beat more slowly Beats faster & stronger

Relaxes airways, which

Constricts airways lets you breathe more
deeply

Stimulates digestion Inhibits digestion

Reduces blood flow Increases blood flow to

to skeletal muscles skeletal muscles

Module 1 | Respiratory and Nervous System

Sympathetic vs Parasympathetic Nervous System
SYMPATHETIC NERVOUS SYSTEM
● Prepares the body for actions and stress (‘Fight or Flight’)
● Neurotransmitters are epinephrine (adrenaline) and
norepinephrine (noradrenaline)
● Structure: The receptors are adrenergic receptors or
adrenoceptors
● Adrenergic drugs, drugs that mimic or interfere with the
functioning of the sympathetic nervous system by
affecting the release or action of
norepinephrine and epinephrine. For example: salbutamol,
dopamine etc
-Function: Dilation of bronchioles (bronchodilation), and
vasoconstriction
Adrenergic antagonists, block or inhibit the release or
activity of epinephrine/norepinephrine. For example:
atenolol, etc
Module 1 | Respiratory and Nervous System
17
PARASYMPATHETIC NERVOUS SYSTEM
● Conserves energy, non-immediate response (‘Rest &
Digest’)
● Neurotransmitter is acetylcholine
● Structure: The Ach receptor subtypes are muscarinic and
nicotinic
● Cholinergic drugs, enhance, or mimic the action of Ach.
For example: nicotine
● Anticholinergic drugs inhibit Ach in CNS and PNS. They
combine reversibly with muscarinic cholinergic receptors,
and prevent access of Ach at these sites. For example:
ipratropium, atropine, scopolamine etc
- Function: Increased heart rate, bronchodilation and
decreased bodily secretions
 Receptors of Parasympathetic Nervous System 18
A RECEPTOR is a protein molecule that receives chemical signals from outside the cell.
When such chemical signals bind to a receptor, they cause some form of cellular/tissue response.

Receptors of Parasympathetic Nervous System

MUSCARINIC RECEPTOR SUBTYPES NICOTINIC RECEPTOR SUBTYPES

Module 1 | Respiratory and Nervous System

 Receptors of Sympathetic Nervous System 19

Type Tissue Actions

Most vascular smooth muscles Contraction

Alpha1 Pupillary dilator muscle Mydriasis
Heart Increase force of contraction
Adrenergic nerve terminals Inhibition force of contraction
Alpha2
Platelets Aggregation
Beta1 Heart Increased rate and force of contraction
Respiratory, uterine, & vascular smooth muscle Relaxation
Beta2
Human liver Glycogenolysis
Beta3 Fat cells Lipolysis

Module 1 | Respiratory and Nervous System

 Mechanism of Action 20

Module 1 | Respiratory and Nervous System

Asthma- An overview 22

Module 2 | Common Diseases Asthma and COPD Global Initiative for Asthma-GINA 2018
Asthma- An overview 23

Module 2 | Common Diseases Asthma and COPD Global Initiative for Asthma-GINA 2018
Risk factors associated with ASTHMA 24

Domestic or
occupational
Viral Tobacco allergens (e.g
infection smoke house dust mites,
pollens,
cockroaches)

Drugs like beta

blockers, aspirin Stress
Exercise
or other NSAIDs

Module 2 | Common Diseases Asthma and COPD

Normal Vs. Asthmatic airways 25

(A) (B) Normal (C) During Asthma

Airway Symptoms

Narrowed airway
(limited air flow)
Muscle
Tightened muscles
constrict airway
Airway
Airways Inflamed/thickened
wall
airway wall
Mucus

Muscle Thickened airway wall

Airway
wall

Lungs Airway x-section Muscle Mucus

Module 2 | Common Diseases Asthma and COPD
 Types of Asthma- GINA 2018 26
The 2018 Global Initiative for Asthma (GINA) guidelines categorize asthma severity as mild, moderate, or severe.
Severity is assessed from the level of treatment required to control symptoms and exacerbations, as follows :

Global Initiative for Asthma-GINA 2018

Module 2 | Common Diseases Asthma and COPD
Types of Asthma- GINA 2018
MILD or MODERATE
● Talks in phrases, prefers
sitting to lying, not agitated
● Respiratory rate increased
● Accessory muscles not
used
● Pulse rate 100-120 beats
per minute
● Oxygen saturation (on air)
90-95%
● PEF >50% predicted or
best
Module 2 | Common Diseases Asthma and COPD
27
SEVERE LIFE - THREATENING
● Talks in words, agitated
● Respiratory rate >30/min ● Drowsy, confused or
● Accessory muscles in use silent chest
● Pulse rate >120 beats per
minute
● Oxygen saturation (on air)
<90%
● PEF ≤50% predicted or
best
Global Initiative for Asthma-GINA 2018
 COPD- An overview 28

Module 2 | Common Diseases Asthma and COPD Global Initiative for Chronic Obstructive Lung Disease-GOLD 2018
 COPD- An overview 29

Module 2 | Common Diseases Asthma and COPD Global Initiative for Chronic Obstructive Lung Disease-GOLD 2018
Risk factors associated with COPD 30

Including cigarette, pipe, cigar, water-pipe and other types of tobacco smoking popular in many
countries.

From biomass fuel used for cooking and heating in poorly vented places.

Including dusts, chemical agents and fumes

Module 2 | Common Diseases Asthma and COPD Global Initiative for Chronic Obstructive Lung Disease-GOLD 2018
Risk factors associated with COPD (Cont.) 31

Aging and female gender increase COPD risk.

Any factor that affects lung growth during gestation and childhood.

Asthma may be a risk factor for the development of airflow limitation and COPD.

Module 2 | Common Diseases Asthma and COPD Global Initiative for Chronic Obstructive Lung Disease-GOLD 2018
COPD classification according to GOLD guidelines 2018 32

Classification of airflow limitation severity in COPD (based on post-bronchodilator FEV 1)

In patients with FEV1/FVC < 0.70:

GOLD 1: Mild FEV1 > 80% predicted

GOLD 2: Moderate 50% < FEV1 < 80% predicted

GOLD 3: Severe 30% < FEV1 < 50% predicted

GOLD 4: Very Severe FEV1 < 30% predicted

Module 2 | Common Diseases Asthma and COPD Global Initiative for Chronic Obstructive Lung Disease-GOLD 2018
Normal Vs. COPD airways 33

Bronchioles lose
Bronchioles their shape Walls of alveoli
(tiny always) and are destroyed, forming
become fewer larger alveoli
Airways Trachea clogged
(windpipe) with mucus
Left lung
Right
lung
Alveoli
(air sacs)

Lung cross-section
Detailed view with COPD

Normal lungs COPD Lungs

Module 2 | Common Diseases Asthma and COPD

Asthma Vs COPD
Asthma
• Onset often early in life; most common
chronic disease in children
• Allergy, rhinitis and/or eczema are also
present
• Reversible airway obstruction
• Episodic
• Most asthmatics are allergic to
airborne allergens such as dust mite,
animal dander, pollens, molds
• Symptoms vary widely from day to day
Module 2 | Common Diseases Asthma and COPD
34
COPD
• COPD occurs in older patients
• Comprises of bronchitis and
emphysema
• Persistent airway obstruction
• Associated with progressive,
severe loss of pulmonary
function over time
• Mostly due to chronic cigarette
smoking
• Symptoms are slowly progressive
 Diagnosis of Asthma and COPD 35
• For the diagnosis of asthma and COPD, the HCPs rely on medical history,
physical exam, and other tests.
• Spirometry is a common test to measure lung volume and flow rates in order
to diagnose abnormal lung function.
• FEV- Forced Expiratory Volume: Patient inhales as deeply as possible, then
exhales forcefully and completely into mouthpiece connected to a
spirometer. FEV1 is a measure of forced expiratory volume in the first second
of exhalation.

Volume (I)
• FVC- Forced Vital Capacity: Max volume of air exhaled with max effort after
max inspiration.
• The ratio of FEV1 to FVC can be useful to identify obstructive, restrictive,
and combined (obstructive-restrictive) defects.

Normal Airways Airway Time (sec)

Obstruction

FEV >80% <80%

FEV1/FVC >0.7 <0.7

Module 2 | Common Diseases Asthma and COPD

Treatment objectives 38

Relieve symptoms, improve health status

Prevent disease progression

Improve exercise tolerance

Prevent recurrent exacerbations with minimal need for ED visits or hospitalization

Provide optimal pharmacotherapy with minimal or no adverse effects from medications

Prevent loss of lung function

Reduce mortality

Module 3 | Pharmacological Management Options Global Initiative for Chronic Obstructive Lung Disease-GOLD 2018
Global Initiative for Asthma-GINA 2018
Treatment options common to both Asthma & COPD
Long-term controller
medications
Taken regularly to control symptoms
- ICS (Inhaled
Corticosteroids
- Agonist)
LABA (Long Acting β2
Agonist)
- LAMA (Long Acting
Antimuscarinic Agents)
Module 3 | Pharmacological Management Options
39
Quick-relief
medications
Calm symptoms fast, but last a short
time
-SABA (Short Acting β2
-SAMA (Short Acting
Antimuscarinic Agents)
What is meant by GINA Guidelines? 40
● GINA stands for Global Initiative for Asthma which is a collaborative effort of National
Heart, Lung, and Blood Institute (NHLBI), NIH (USA) and the World Health Organization
(WHO), established in 1993
● Established to increase awareness about asthma and improve its management
● GINA is a worldwide co-ordinated effort that:

Promotes
Prepares Encourages
collaboration on
scientific reports implementation of
asthma research
on asthma recommendations
at an international
scale

Global Initiative for Asthma-GINA 2018

Module 3 | Pharmacological Management Options
 Management of Acute Asthma Exacerbations (GINA): 41

*SABA - Short-acting Beta-2 Agonist

Module 3 | Pharmacological Management Options
Global Initiative for Asthma-GINA 2018
 What is meant by GOLD Guidelines? 42
● GOLD stands for ‘Global Initiative for Chronic Obstructive Lung Disease’
● GOLD was launched in 1997 in collaboration with the National Heart, Lung, and Blood Institute, NIH (USA) and
the WHO
● With the collaboration of leading experts from around the globe, GOLD:

PROMOTES
INCREASES research into increasing
awareness about COPD prevalence, its
COPD being a public link with the
health issue environment and
prevention programs

RECOMMENDS IMPLEMENTS
effective COPD and evaluates
management and effective programs to
prevention strategies decrease COPD
morbidity and
mortality

Global Initiative for Chronic Obstructive Lung Disease-GOLD 2018

Module 3 | Pharmacological Management Options
Management of COPD- GOLD 43
Inhaled bronchodilators in COPD are central to symptom management and commonly given on a regular basis to
prevent or reduce symptoms.

SABA* (eg. salbutamol) or SAMA* (eg. ipratropium)

Regular and as-needed use improves FEV1 and symptoms.

Combination of SABA* (eg. salbutamol) and SAMA* (eg. ipratropium)

Superior compared to either medication alone in improving FEV1 and symptoms.

Combination of LABA* (eg. formoterol) and LAMA* (eg. tiotropium)

Significantly improve lung function, dyspnea, health status, and reduce exacerbation rates.

LAMAs* (eg. tiotropium) have a greater effect on exacerbation reduction compared with LABAs* (eg. formoterol)
and decrease hospitalizations.

Module 3 | Pharmacological Management Options

Global Initiative for Chronic Obstructive Lung Disease-GOLD 2018
Management of COPD- GOLD 44
Combination of LABA* (eg. formoterol) and LAMA* (eg. tiotropium)

Increases FEV1 and reduces symptoms compared to monotherapy.

Combination of LABA* (eg. formoterol) and LAMA* (eg. tiotropium)

Reduces exacerbations compared to monotherapy or ICS/LABA* (eg. budesonide/formoterol).

Tiotropium improves effectiveness of pulmonary rehabilitation in increasing exercise performance.

Theophylline exerts a small bronchodilator effect in stable COPD and that is associated with modest symptomatic
benefits.

*SAMA - Short-acting Anti-muscarinic Agent

*SABA - Short-acting Beta-2 Agonist
*LAMA - Long-acting Anti-muscarinic Agent
*LABA - Long-acting Beta-2 Agonist
*ICS - Inhaled Corsticosteroids

Module 3 | Pharmacological Management Options

Global Initiative for Chronic Obstructive Lung Disease-GOLD 2018
Treatment options common to both Asthma & COPD 45
SHORT ACTING ANTIMUSCARINIC/ANTICHOLINERGIC
(SAMA) INHALED
Ipratropium Bromide
Indications/ Mechanisms Adverse effects Pharmacokinetics & Additional Points
Indications: ● Drying of mouth, ● Onset of action is seen
● Relief of acute within 3-5 mins and
urinary retention or
bronchospasm hypersensitivity. duration of action is 6
● Maintenance treatment hours.
of bronchospasm ● Multiple doses of IB in
associated with COPD the emergency dept.
Mechanisms: provides additive
● Bronchodilation. effects to SABA.
through inhibition of ● May be alternative for
muscarinic cholinergic patients who do not
receptors. tolerate SABA.

Module 3 | Pharmacological Management Options

Treatment options common to both Asthma & COPD Cont.
LONG ACTING ANTIMUSCARINIC/ANTICHOLINERGICS (LAMA) INHALED
Indications/ Mechanisms
Indications:
● Long-term once daily
maintenance treatment
in patients with COPD.
● Indicated as add-on
maintenance treatment
in patients with
asthma.
Mechanisms:
● Bronchodilation
through inhibition of
muscarinic
cholinergic receptors.
Module 3 | Pharmacological Management Options
46
Tiotropium Bromide
Adverse effects Pharmacokinetics & Additional Points
● Drying of mouth, ● Onset of action is seen
within 30 mins and
urinary retention,
duration of action is
headache, abdominal
≥24 hours.
pain, chest pain,
● Hepatic metabolism.
increased wheezing.
● Not indicated as rescue
medication for the
relief of acute
bronchospasm in
COPD and asthma.
Treatment options common to both Asthma & COPD Cont. 47
SHORT-ACTING BETA2- AGONISTS (SABA) INHALED:
Albuterol (Salbutamol) Levalbuterol

Indications/ Mechanisms Adverse effects Pharmacokinetics & Additional Points

● Onset of action is from
Indications: ● Inhaled therapy may 3-5 mins and duration of
● Relief of acute symptoms;
cause adverse action is 6 hours.
quick-relief medication. ● For patients who have
cardiovascular events,
● Preventive treatment for
especially in the intermittent asthma,
EIB (Exercise Induced
elderly. regularly scheduled daily
Bronchospasm) prior to
use is not
exercise.
recommended[2].
Mechanism:
● Bronchodilation through ● For patients frequently
smooth muscle relaxation. using SABA, controller
therapy should be
considered.

Module 3 | Pharmacological Management Options

Treatment options common to both Asthma & COPD Cont. 48
LONG-ACTING BETA2-AGONISTS (LABA) INHALED
Formoterol Salmeterol

Indications/ Mechanisms Adverse effects Pharmacokinetics & Additional Points

Indications: ● May cause anxiety, ● Onset of action is from

● Long-term prevention of
symptoms, added to ICS
(inhaled corticosteroids)
● Prevention of EIB
(exercise induced
bronchospasm).
Mechanisms:
● Bronchodilation through
smooth muscle relaxation.
muscle tremors and
cardiovascular toxicity
with over usage.
● A diminished broncho
protective effect may
occur within 1 week of
chronic therapy.
15-30 mins and duration
of action is 12-24 hours
● Not to be used to treat
acute symptoms or
exacerbations.
● Should not be used as
monotherapy for long-
term control of asthma.

Module 3 | Pharmacological Management Options

Treatment options common to both Asthma & COPD Cont. 49
INHALED CORTICOSTEROIDS (ICS)
Beclomethasone Budesonide

Indications/ Mechanisms Adverse effects Pharmacokinetics & Additional Points

Indications:
● Long-term prevention of ● Oropharyngeal ● Onset of action varies
symptoms; suppression, candidiasis. between different
control, & reversal of members of this class
inflammation. ranging from 1 day to 8
● Oral Prednisolone and IV days. Maximal benefit of
steroids reserved for some members may take
severe acute attacks. 1 to 2 weeks.
Mechanisms:
● Anti-inflammatory.
● Reduce airway
hyperresponsiveness.

Module 3 | Pharmacological Management Options

 51

WHAT IS BFS TECHNOLOGY?

Module 4 | Manufacturing Technology

Blow Fill Seal (BFS) Technology 52

INTRODUCTION:
● BFS technology is a manufacturing technique used to produce small and large volume liquid-
filled parenteral, inhalation and oral products using medical grade plastic.

● Originally developed in Europe in the 1930’s, it was introduced in the United States in the
1960’s.

● It is an advantaged form of aseptic processing as stated by the US Food and Drug

Administration (FDA) in the packaging of pharmaceutical and healthcare products.

Module 4 | Manufacturing Technology

 Blow Fill Seal (BFS) Technology 53
What is BFS?
● Inside BFS machine FDA approved medical grade plastic
is used for making plastic ampoules

● Plastic ampoule is prepared through extruding and

moulding and the product is filled in ampoule then it’s
sealed and final product is available.

● The whole process takes place under sterile filling

chamber where no human interaction takes place.

● Final product produced with aseptic filling and greater

sterility with NO HUMAN INTERACTION.

Module 4 | Manufacturing Technology

 Blow Fill Seal Cycle 54

BLOWING FILLING SEALING

The plastic resin is heat extruded
into the opened blow mold. The
mandrel is lowered onto the neck
of the mold and uses compressed
air to blow the tube section into
the container shape.
The container is filled with
the precise product amount
as measured by the dosing
system, again via the
mandrel.
The mandrel is removed, the
head mold closes, and the
required seal is formed by a
vacuum. The blow mold opens,
the container leaves the machine,
and the next cycle begins.

Module 4 | Manufacturing Technology https://www.rommelag-engineering.com/en/bfs/

 55

Module 4 | Manufacturing Technology

 Plastics 56
Plastic is material consisting of any of a wide range of synthetic or semi-synthetic organic compounds that can be molded into solid
objects.
TYPES ABOUT APPLICATIONS

● Graded according to density into LDPE &

HDPE ● Implants
POLYETHYLENE (PE) ● Greater rigidity ● Plastic bags
● High melting temperatures ● Healthcare appliances

● Not common, has similar properties to PE ● Surgical trays

POLYPROPYLENE (PP) ● Has better resistance to high temperatures ● Widely used for making closures
● More brittle at lower temperatures than PE ● Furnitures

● Variety of grades available ● Blood bags and tubings

POLYVINYL CHLORIDE ● Used for flexible or rigid packaging
● Water pipes
(PVC) depending upon grades
● Blisters to protect medicines
● Plasticized or unplasticized

● Hard, only used for rigid packs ● Toys

● Not suitable for liquid and semi-solid
POLYSTYRENE (PS) formulations ● Bottles and jars
● Has poor resistance to certain chemicals ● Automobile parts
Module 4 | Manufacturing Technology
 Low Density Polyethylene (LDPE): 57
● Low-density polyethylene is a thermoplastic made from the monomer ethylene
Properties:
❏ Semi rigid
❏ Translucent
❏ Good chemical resistance
Hudson Pharma:
● We use medical grade plastic (Bormed LE6609-PH) in our blow fill seal process, approved for making
ampoules for injectable solutions. The plastic is
-Additive free
-Odourless
-Stable thermoplastic (melting temperature of 117°C), with
-No chemical reactivity
● European Pharmacopoeia (EU) and United States Pharmacopeia (USP) compliant

Module 4 | Manufacturing Technology

 Stability Studies 58
Stability testing provides evidence of how the quality of an Active Pharmaceutical Ingredient (API) or
Finished Pharmaceutical Product (FPP) varies with time under the influence of a variety of environmental
factors such as temperature, humidity and light.
In general, an API should be evaluated under storage conditions that test its thermal stability and, if
applicable, its sensitivity to moisture. The storage conditions and the lengths of studies chosen should be
sufficient to cover storage, shipment, and subsequent use.

GENERAL CASE:

Study Storage Conditions Minimum time period covered by data

at submission
Long term 30°C ± 2°C/65% RH ± 5% RH 12 months

Accelerated 40ºC ± 2ºC/75% RH ± 5% RH 6 months

-These guidelines are given by The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH)

Module 4 | Manufacturing Technology

 What is Combihale? 60
(Ipratropium 0.5mg/Salbutamol 2.5mg)

● COMBIHALE is a DUAL ACTION combination nebulization

solution of Ipratropium bromide (anticholinergic) and Salbutamol
(beta-receptor agonist)

● It is manufactured by BFS technology, an advantaged filling process

as stated by US FDA

● It is a preservative free, clear, colorless solution

● Available in respules of 2.5 ml, packs of 5s and 20s

● MRP of COMBIHALE 5s pack is Rs. 345.00/ TP Rs. 293.25

● MRP of COMBIHALE 20s pack is Rs. 1,324.80/ TP Rs. 1,126.08

Module 5 | Combihale (Ipratropium Bromide + Salbutamol)

COMBIHALE 61
GREATER
bronchodilation
than TWICE the
dose of
monotherapy (The
Chest)

DUAL ACTION
therapy offering An ideal RESCUE
synergistic THERAPY for
response significant
ADDITIONAL
bronchodilation
(The Lancet)

Module 5 | Combihale (Ipratropium Bromide + Salbutamol)

Advantages of Combination Therapy
2 62

The Chest

Journal of Asthma

The Lancet

Module 5 | Combihale (Ipratropium Bromide + Salbutamol)

How Combination Works? 63

Module 5 | Combihale (Ipratropium Bromide + Salbutamol)

The efficiency of dual therapy (Combihale) over monotherapy in asthmatic patients 64

Module 5 | Combihale (Ipratropium Bromide + Salbutamol)

The efficacy of nebulized combination therapy vs either component alone in COPD patients 65

Module 5 | Combihale (Ipratropium Bromide + Salbutamol)

 Product Advantages 66

The Lancet
The Lancet

US FDA
British Journal of Clinical The Chest
Pharmacology

Module 5 | Combihale (Ipratropium Bromide + Salbutamol)

 Product Information 67

Module 5 | Combihale (Ipratropium Bromide + Salbutamol)

 Product Information (Cont.) 68

Module 5 | Combihale (Ipratropium Bromide + Salbutamol)

 Special Population 69
Pediatrics:
The efficacy and safety in children and adolescents under 12 years has not been established. COPD does not occur
in children under 18 years of age.
Hepatic Insufficiency:
This medication has not been studied in patients with hepatic insufficiency.
Renal Insufficiency:
This medication has not been studied in patients with renal insufficiency.
Geriatrics:
Elderly patients can use this medication at the recommended dose.
Pregnant Women:
Pregnancy category C

The safety of this combination medicine in pregnancy has not been established. There is no adequate and well-
controlled studies of combination of ipratropium bromide and salbutamol sulfate in pregnant women. Combination
should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.

Module 5 | Combihale (Ipratropium Bromide + Salbutamol)

COMBIHALE vs Ventolin 70

COMBIHALE
● Dual bronchodilator activity offers synergistic
action
● Greater bronchodilation due to presence of two
bronchodilators
● Preservative free
● No adverse effects; as Combihale is completely
free from preservatives[1]
● Reduced COPD exacerbations[2]
VENTOLIN
● Single bronchodilator activity
● Lesser extent of bronchodilation due to single
bronchodilator
● Benzalkonium chloride used as preservative
● BAC causes adverse effects like paradoxical
bronchoconstriction in asthmatic patients[3]
● More chances of COPD exacerbations[2]

The Lancet 1989

[1]

The Chest 1999

[2]

The Journal of Human Pharmacology 1998, Journal of Clinical Immunology 2001

[3]
Module 8 | The Sales Pitch
 Pregnancy Categories 71

CATEGORY A Controlled studies show no risk or find no evidence of harm.

CATEGORY B Animal studies show no risks, but there are no controlled studies on pregnant
women.
CATEGORY C Animal studies have shown risk to the fetus, there are no controlled studies in
women, or studies in women and animals are not available.

CATEGORY D There is positive evidence of potential fetal risk, but the benefits from use in pregnant
women may be acceptable despite the risk (i.e. life threatening condition to mother).
Studies in animals or human beings have demonstrated fetal abnormalities, or there
CATEGORY X
is evidence of fetal risk. The drug is contraindicated in women
who are or may become pregnant.

Module 5 | Combihale (Ipratropium Bromide + Salbutamol)

 Inhalation devices 73

Inhaled medicines go directly to the lungs. There are fewer side effects than medicines taken by mouth.
Inhaled may be anti-inflammatory or bronchodilating or both. The devices are:

Nebuliser

Metered Dose Inhaler

Dry Powder Inhaler/ Rotary

Inhaler

Module 6 | Dosage Form & Administration Techniques

 Inhalation devices
Nebulizer
-A nebulizer is a device
that sprays a fine mist of
medicine.
-A mouthpiece or mask is
connected to a machine
via plastic tubing to deliver
medicine.
-Different kinds of
nebulizers are available.
-Knowing how to use and
clean a nebulizer is
important.
Module 6 | Dosage Form & Administration Techniques
Metered Dose
Inhaled (MDI)
-It uses a chemical to push
the medicine out of the
inhaler.
-MDIs are held in front of
or inserted into the mouth
as the medicine is released
in puffs.
74
Dry Powder Inhaler/
Rotary Inhaler
-These inhalers deliver
dry powdered medicine
as a person breathes
-DPIs utilize your own
breath to deliver
medication into your
lungs rather than a
propellant. The
medication in DPIs is
not an aerosol but is
contained in a pill or
capsule that is
punctured and inhaled.
 Inhalation devices 75
Metered Dose Dry Powder Inhaler/
Nebulizer Rotary Inhaler
Inhaled (MDI)
-Easier for younger children and
adults to use. -Portable, hand-held
-For the whole family canisters -No propellant used
- Drug is directly delivered to the - Ready to use -Portable, compact
airways and helps to speed up the
action of the medicine in the lungs.
-Dramatic improvement in quality of
life for some asthmatics. -Young children and
-Can be delivered to unconscious asthmatics suffering an
patients -Spacers are needed acute attack may not be
-No technique required -Poor technique leads to able to produce a deep
decreased medicine intake enough breath to use a
-Difficulty in determining DPI effectively.
-Cleaning/disinfection remaining doses -Children and older
needed after use -Children and older people people struggle using
struggle using MDIs DPIs

Module 6 | Dosage Form & Administration Techniques

How to use a Nebulizer 76

Module 6 | Dosage Form & Administration Techniques

The Final Pitch 78

Combihale is a
DUAL ACTION
therapy with a
synergistic
response
clinical score as compared to
Combihale is preservative
free. According to British
Journal Of Clinical
Pharmacology, preservative-
free product limits side-
effects and increases efficacy.
Module 7 | The Final Pitch
Provides greater Combihale is supplied
bronchodilation than twice as nebulizing solution
the dose of monotherapy, which is the most
decreased hospital beneficial delivering
admissions and improved method according to
Respiratory care
salbutamol in moderate to
severe asthmatic
exacerbations.
Ipratropium is a short acting
anticholinergic agent and
salbutamol is a short acting
beta agonist, combining these
two medication in a single
dosage form provides greater
bronchodilation and improved
pulmonary function.
The Final Pitch (Cont.)
Combihale is packaged
into 0.5mg/2.5mg 2.5
ml respules in packs of
5s and 20s, priced at
345 and 1,324.80 MRP
respectively.
Use of ingredients
and plastic from FDA
approved sources to
ensure safety.
Module 7 | The Final Pitch
79
Combihale is indicated for
Combihale is patients suffering from
manufactured by BFS asthmatic attacks and
technology which is an bronchospasms associated with
FDA approved advantaged COPD. It is used via nebulizer by
those patients who are unable to
filling process.
use MDIs such as elderly and the
incapacitated ones.
Dose for adults (including
elderly patients and children
over 12 years): 1 single dose
unit three or four times daily.
Combihale have the mean
duration of action of about 6-8
hours.
 Launch Plan - COMBIHALE 81

PRESCRIPTION COMBIHALE
VISION ANALYSIS LAUNCH STRATEGY

Module 8 | The Sales Pitch

Sals Yearly Data Analysis JUL 15 - JUN 16 82

• Total Pharma Market 328 Billion Growth 10%

• Antiasthmatics and COPD products 7.9 Billion Growth 20 %

• Anticholinergics combinations with B2-stimulants,

inhalants 52 Million Growth 21%

Module 8 | The Sales Pitch

Competition- (Ipratropium Bromide + Salbutamol) 83

RETAIL Market MARKET

NAME DOSE DOSAGE PACK SIZE PRICE Value SHARE GROWTH
FORM (PKR) (PKR) (Nebulization (%)
Solution %)

Atem 2 ml Inhalation 352

5 vial x 2ml 289.00 95.7 34
(Chiesi) (0.025% w/v) soln Million

Sprahaler Inhalation
(Highnoon) 500 mcg/2 ml soln 5 vial x 2 ml 275.00 - - -

Ventolin
100 mg/20 Inhalation 20ml
Respirator 35.00 77 Million 96.5 14.0
ml soln 1s
(GSK)
 IMS Data Analysis - Doctor’s Specialty 84
PRESCRIPTION % BY DOCTORS' SPECIALTY
Doctor's Type Atem Ventolin
Ipratropium Bromide Salbutamol
% %
Total Prescriptions 744,000 8,043,000
G.P 42.0 50.5
Physician 29.4 10.5
Pediatric 9.4 3.7
Surgery 0.0 0.2
Gynae 2.5 1.4
Dermatologist 0.0 0.0
EENT 0.3 0.4
RMO 12.4 33.3
Cardiologist 4.0 0.1
Psychiatrist 0.0 0.0
Total 100 100.1
Module 8 | The Sales Pitch
 Target Customer Segmentation 85

• General Physicians

• Pulmonologists

• RMOs

• Emergency Rooms/Casualty

• Medicine Wards

Module 8 | The Sales Pitch

COMBIHALE vs Ventolin 86

COMBIHALE
● Preservative free
● No adverse effects; as Combihale is completely
free from preservatives[1]
● Greater bronchodilation due to presence of two
bronchodilators
● Reduced COPD exacerbations[2]
● Dual bronchodilator activity offers synergistic
action
VENTOLIN
● Benzalkonium chloride used as preservative
● BAC causes adverse effects like paradoxical
bronchoconstriction in asthmatic patients[3]
● Lesser extent of bronchodilation due to single
bronchodilator
● More chances of COPD exacerbations[2]
● Single bronchodilator activity

The Lancet 1989

[1]

The Chest 1999

[2]

The Journal of Human Pharmacology 1998, Journal of Clinical Immunology 2001

[3]
Module 8 | The Sales Pitch
 Strategic Plan - Phase-1 87

● Submit the relevant chemist list of all targeted doctors to your distributor for
Combihale availability.
● All BMs and RSMs are advised to maintain good relations with formulary
committee doctors of all teaching and non-teaching hospitals to ensure the
inclusion of Combihale in their hospital formularies and tenders.
● All RSMs will meet with their respective distributor’s salesmen and brief them on
Combihale, i.e It is a DUAL action drug with a synergistic response, superior to
Atem and Ventolin as it is preservative free and unit-dose. This will increase the
confidence of the salesmen and will help make our product available in the
market.
● Additionally ensure the availability of Combihale at the important centralized
chemists and chain of pharmacies like Shaheen, Fazal Din, Pharmax etc
● All RSMs, BMs, and, SMs are advised to monitor and ensure the daily availability
of Combihale at their targeted chemist.

Module 8 | The Sales Pitch

 Strategic Plan - Phase-2 88

● Each SPO will target 50 Customers

Selection Criteria:
I. The Doctors whom you have good relation with.
II. The Doctors whom the RSMs have good relations with.
III. The Doctors who are friendly in nature.
IV. The Doctors who like to Rx new products.
V. The Doctors who love to conduct trial and like heavy sampling.
VI. The Doctors who like persistent and regular visits.
VII. The Doctors who like good gifting.

Module 8 | The Sales Pitch

 Chamber Strategy 89

• Before visiting the doctor, ensure that Combihale is available at his/her nearby
medical store as per your submitted list.
• Introduce yourself to the doctor and request 5 uninterrupted minutes from
his/her busy schedule, as you have a new product to introduce.
• Detail Combihale and establish that Combihale is the only Ipratropium Bromide
and Salbutamol combination in Pakistan that offers a synergistic effect. If the
doctor is newly added to your list, ask to run a 3 minute video so that you can
introduce Hudson pharma.
• After the video, present the gift, drop the sample and take commitment that the
doctor will share his/her experience of using Combihale when you will visit
him/her next time. Also, inform him about the availability of product at his/her
nearby medical stores.

Module 8 | The Sales Pitch

 Sales Call Planning 90
-
FIRST CALL
Detail product with tablet, drop literature and 4 product samples. Mark all samples and
gifts in CRM.

SECOND CALL
Detail Combihale, drop pens and ask for any experience using Combihale.

THIRD CALL

Detail Combihale through tablet, drop literature and 2 samples.

FOURTH CALL

Detail Combihale , drop 2 Rx pads and ask for experience.

NOTE: Mark ALL samples, promotional items and gifts in the CRM.

Module 8 | The Sales Pitch

Glossary 91
Abdomen The body space between the thorax (chest) and pelvis

The chief neurotransmitter of the parasympathetic nervous system.

Acetylcholine (Ach)

Action potentials The electrical impulses (messages) that travel throughout the nervous system through neurons.

Adolescence Adolescence typically describes the years between ages 13 and 19 and can be considered the transitional stage from childhood to adulthood.

Adrenal medulla The adrenal medulla, the inner part of an adrenal gland. The main hormones secreted by the adrenal medulla include epinephrine (adrenaline) and
norepinephrine (noradrenaline).

Aggregation The formation of a number of things into a cluster.

Agitate Make (someone) troubled or nervous.

Anticholinergic drugs Inhibit Ach in CNS and PNS.

Aseptic Free from contamination caused by harmful bacteria, viruses, or other microorganisms.

Asthma Chronic lung disease that inflames and narrows the airways.

Axon long projection of a nerve cell, or neuron.

 Glossary 92
Bioavailability Bioavailability refers to the extent and rate at which the active moiety (drug or metabolite) enters systemic circulation, thereby accessing the site of action.

Biomass Organic material that comes from plants and animals

Bloodstream The blood circulating through the body of a person or animal.

Brainstem
The brainstem is the posterior part of the brain

Breathing
Involves external respiratory system to take in O 2 & release CO2

Bronchitis Inflammation of the bronchial tubes

Bronchodilator A bronchodilator is a substance that dilates the bronchi and bronchioles, decreasing resistance in the respiratory airway and increasing airflow to the lungs

Bronchospasm Bronchial spasm is a sudden constriction of the muscles in the walls of the bronchioles.

Cardiac tachyarrhythmias Defined as abnormal heart rhythms

cAMP Cyclic adenosine monophosphate is a second messenger important in many biological processes.
 Glossary 93
Capillaries A capillary is a small blood vessel

Cellular respiration Release of energy from food substances in living cells.

Cholinergic Enhance, or mimic the action of Ach

Cerebellum The cerebellum is the area found at the back and bottom of the brain.

Cerebrum The principal and most anterior part of the brain

Chronic bronchitis Bronchitis is an inflammation of the bronchial tubes, the airways that carry air to your lungs. It causes a cough that often brings up mucus

Collaboration The action of working with someone to produce something.

COPD COPD is the most prevalent indication of obstructive lung disease and mainly comprises of chronic bronchitis (inflammation of bronchial tubes) and emphysema
(damage to the alveoli).
Glossary 94
Coughing Foreign bodies or irritants in the nasal passage are forced out of the respiratory tract through coughing or even sneezing.

Dendrites A short branched extension of a nerve cell, along which impulses received from other cells at synapses are transmitted to the cell body.

Desensitization Insensitive

Drug Clearance Drug clearance is concerned with the rate at which the active drug is removed from the body

Dysfunction Abnormality or impairment in the operation of a system.

Dyspnea Shortness of breath

Eczema Condition where patches of skin become inflamed, itchy, red, cracked, and rough.

Effector cells Effector cells are the relatively short-lived activated cells

Embolism An embolism is a blocked artery caused by a foreign body, such as a blood clot or an air bubble.
 Glossary 95
Emphysema In emphysema, the tiny air sacs (alveoli) at the end of the airways in the lungs are damaged.

Gestation Gestation is the period of time between conception and birth.

Glycogenolysis Glycogenolysis is the breakdown of glycogen into glucose.

FEV Forced Expiratory Volume: A common test to measure lung volume and flow rates in order to diagnose abnormal lung function.

FVC Forced Vital Capacity: Max volume of air exhaled with max effort after max inspiration.

Ganglia
Ganglia are part of peripheral nervous system. They work as relay station for nerve signals

Gaseous Exchange is the delivery of oxygen from the lungs to the bloodstream, and the elimination of carbon dioxide from the bloodstream to the lungs.

The plasma concentration of a drug is halved after one elimination half-life.

Half-life

A hermetic seal is the quality of something—a container, structure, etc.—being airtight (excluding passage of air, oxygen, or other gases)
Hermetic Seal
 Glossary 96
Amount of water vapour present in air
Humidity

Sit or stand with one's shoulders raised and the top of one's body bent forward.
Hunch

Airway hyperresponsiveness is a characteristic feature of asthma and consists of an increased sensitivity of the airways to an inhaled constrictor agonist
Hyperresponsiveness

A condition in which a portion of the heart becomes thickened without an obvious cause.
Hypertrophic cardiomyopathy

Incapacitate To make someone unable to work or do things normally, or unable to do what they intended to do

Intensive care Intensive care is needed if someone is seriously ill and requires intensive treatment and close monitoring, or if they're having surgery

Internal Respiration Exchange of substances between capillaries and cells.

Larynx The larynx, commonly called the voice box, is an organ in the top of the neck involved in breathing, producing sound, and protecting the trachea against food
aspiration.
 Glossary 97
Liberation Release

Lipolysis The breakdown of fats and other lipids to release fatty acids.

Mandrel A mandrel is an object used to shape machined work

Monomer A molecule that can be bonded to other identical molecules to form a polymer.

Monotherapy The treatment of a disease with a single drug.

Morbidity The condition of being diseased.

Mortality A measure of the number of deaths in a particular population, scaled to the size of that population, per unit of time.

Mydriasis Dilation of the pupil of the eye

Narrow angle glaucoma Occurs suddenly, when the colored portion of your eye (iris) is pushed or pulled forward. This causes blockage of the drainage angle of the eye.
 Glossary 98
Neuromuscular junction The neuromuscular junction is the site of communication between motor nerve axons and muscle fibres

Neuron The basic unit of the nervous system is called a neuron. Individual nerves are made up of thousands of neurons.

Neurotransmitter Chemical messengers, that enable neurotransmission.

Smell occurs when airborne molecules drawn into nasal cavity.

Olfaction

Any living biological entity, such as an animal, plant, fungus, or bacterium.

Organism

Fungal infection of oral cavity (mouth)

Oropharyngeal candidiasis

The fraction of oxygen-saturated hemoglobin relative to total hemoglobin (unsaturated + saturated) in the blood (95-100%)
Oxygen Saturation Rate

Paradoxical bronchospasm Defined as the rapid onset of unexpected bronchospasm occurring shortly after the administration of an inhalation aerosol.

pH pH is a scale used to specify the acidity or basicity of a solution

Glossary 99
Pharmacokinetics Pharmacokinetics is the branch of pharmacology concerned with the movement of drugs within the body. What the body does to the drug

Plasticize Make plastic or mouldable, especially by the addition of a plasticizer.

Platelets Platelets are tiny blood cells that help your body form clots to stop bleeding

Preservative Help prevent the growth of microorganisms, particularly bacteria and fungi, which may cause disease or infection.

Prevalence Prevalence is a statistical concept referring to the number of cases of a disease that are present in a particular population at a given time

Pulse rate Pulse rate is the number of heartbeats per minute.

Receptors Protein structures when bound to chemical signals cause cellular change.

Reflex action Reflex actions are rapid and happen without us thinking.

Regulation of blood pH Altered by changing blood carbon dioxide levels Carbonic acid Buffer system.

Rehabilitation
Rehabilitation is the process that assists a person in recovering from a serious injury, illness or surgery to regain strength

Respiration
Respiration is the process by which an organism takes in oxygen (inhalation) and releases carbon dioxide (exhalation).
 Glossary 100
Respiratory rate The number of breaths you take per minute (Adults 12-20 breaths/min)

Respiratory System
It is a set of organs involved in the exchange of carbon dioxide and oxygen between a body and its environment.

Rhinitis
Irritation and inflammation of the mucous membrane inside the nose.

Sensory Neuron Respond to stimuli such as light and sound.

Spacers A spacer is a large plastic or metal container with a mouthpiece and a hole for the aerosol inhaler.

Spirometry A common test to measure lung volume and flow rates in order to diagnose abnormal lung function.

Sterile Free from living germs or microorganisms

Synapse synapse is a structure that permits a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or to the target effector cell.

Synaptic terminal An area at the end of an axon that contains neurotransmitters.

Synergistic To work together to provide enhanced effect

Thermoplastic Substances that become plastic on heating and harden on cooling, and are able to repeat these processes.
 Glossary 101
Thermoregulation Heating and cooling of body.

Unplasticized Not made plastic

Vocalization Enables production of sound and speech.

Volume of distribution Amount of drug in tissues other than blood.

Wheezing A high-pitched whistling sound made while breathing.

 FAQ’s 103
1. Why should I prescribe your product?
Our product COMBIHALE have many unique features like:
- Preservative free which limits the side effects
- Manufactured by BFS technology which is stated as advantaged filling process by U.S. FDA
- Breakage free plastic ampoules which provides greater assurance of sterility by eliminating glass shards
- Provides dual and synergistic action due to presence of two bronchodilators
- An ideal rescue therapy which provides greater bronchodilation than monotherapy
- Unit dose vials prevent the product from contamination
1. How is COMBIHALE different from the others (Atem, Ventolin, Ipratec)?
- COMBIHALE is a combination product containing two bronchodilators which are Ipratropium Bromide and
Salbutamol
- The two bronchodilators offer dual action and greater bronchodilation than monotherapy
- COMBIHALE is a preservative free product which limits the side effects and increases efficacy
1. Advantages of nebulizers over MDIs and DPIs?
- Nebulizers are easier for young children and adults to use
- Can be delivered to unconscious patients
- A device for the whole family
 FAQ’s 103
4. What are the advantages of unit-dose vials over multi-dose vials?
- Unit dose vials lead to better patient outcomes due to prevention of contamination as in multi dose vials
- Unit dose vials lead to fewer medication errors due to accurate dosing
- They are cost saving
5. What is BFS technology? How is it different from others?
It is an advantaged form of processing as stated by the U.S. Food and Drug Administration (FDA) in the
packaging of pharmaceutical and healthcare products. The whole process (blowing, filling and sealing)
takes place under sterile filling chamber in one single cycle where no human interaction takes place.
6. What type of plastic you use for making ampoules?
We use medical grade plastic (Bormed LE6609-PH) in our blow fill seal process, approved for making
ampoules for injectable solutions. The plastic is
-Additive free
-Odourless
-Stable thermoplastic (melting temperature of 117°C), with
-No chemical reactivity
 FAQ’s 103
7. How are you bringing safety and innovation to the industry?
We are bringing the unique manufacturing technology in the pharmaceutical industry of Pakistan that is BFS
technology. In which the whole process (blowing, filling and sealing) is carried out in a single cycle under
sterile filling chamber where no human interaction takes place. This technology is stated as an advantaged
filling process by U.S. FDA.
8. How combination therapy is better than monotherapy?
Combination therapy provides greater bronchodilation by acting on both proximal and distal airways of lungs
and hence provides the total lung coverage.
9. What is the dose of COMBIHALE?
COMBIHALE is a DUAL ACTION combination nebulization solution of Ipratropium bromide 0.5 mg
(anticholinergic) and Salbutamol 2.5 mg (beta-receptor agonist) available in respules of 2.5 ml, packs of 5s. It
is manufactured by BFS technology, an advantaged filling process as stated by US FDA.
10. What is the paeds dose for ipratropium?
Neonates: 25 mcg/kg/dose 3 times daily
Children: 0.25 to 0.5 mg every 6 to 8 hours.
 FAQ’s 103
11. What is the paeds dose for salbutamol (mg/kg)?
Infants & Children <5 years: 0.63 to 2.5 mg every 4 to 6 hours.
Children ≥5 years & Adolescents: 1.25 to 5 mg every 4 to 8 hours.
12. What is the price difference between your product and others available in same dosage forms (i.e nebulizers)?
- Atem (Ipratropium Bromide ONLY) having the price of 300 rs and available in pack of 5 UNIT DOSE VIALS of
2 ml
- Ventolin Respirator (Salbutamol ONLY) having the price of 35 rs and available in 20 ml MULTI DOSE bottle
- COMBIHALE (Ipratropium Bromide and Salbutamol BOTH) having the price of ONLY 300 rs and available in
pack of 5 UNIT DOSE VIALS of 2.5 ml
13. How does your product being preservative-free is beneficial to the patients ?
Our preservative free products increase the efficacy and limit the chances of side effects like paradoxical
bronchoconstriction in patients using products (Ventolin) containing benzalkonium chloride as a preservative.
14. VENTOLIN contain preservatives (BAC and EDTA)?
Ventolin contains Benzalkonium Chloride (BAC) as a preservative and it causes paradoxical bronchoconstriction
in asthmatic patients.
 FAQ’s 103

15. What is the difference between paradoxical bronchoconstriction and rebound congestion?
- Paradoxical bronchoconstriction is defined as the rapid onset of unexpected bronchospasm occurring
shortly after the administration of a medicine
- Rebound congestion is a constant nasal stuffiness (congestion) that develops from the overuse of nasal
sprays or drops or gels that contain a decongestant medicine
16. What is the mode of action of COMBIHALE and how it different from VENTOLIN?
- Combihale is a combination product containing two bronchodilators which are Ipratropium Bromide
(anticholinergics), acting on M3 receptors in the proximal airways and Salbutamol (beta agonist), acting on
beta-2 receptors in the distal airways. Hence provides greater bronchodilation by total lung coverage
- Ventolin contains Salbutamol ONLY which acts in the distal airways.