Formulation and development of sublingual tablet

Presentation by- Name of Guide

-
Neha Bhagwat Yenge Prof. K.N Tarkase
M Pharm 2nd year(3rd sem) Dep. Of Pharmaceutical

(Pharmaceutical Quality Quality Assurance

Assurance) Roll no. -17
Academic year 2022-23

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Dr. Vithalrao Vikhe Patil Foundation of Pharmacy, Ahmednagar.
 CONTENTS-
 Introduction
 Aim
 Need of work
 Plan of work
 Literature review
 Preformulation studies
 Evaluation test for formulation
 Stability studies
 Hypothesis of work
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 References
Introduction :

 Sublingual tablet -Sublingual tablets are those tablets that are placed beneath
the tongue where they can dissolve or disintegrate quickly and are absorbed
directly without passing into GIT.
 Sublingual route -It is pharmacological route of administration by which drug
diffuse into the blood through tissues under the tongue.
 Systemic delivery of drugs through the - mucosal membranes lining the
floor of the mouth to the systemic circulation
 When sublingual tablets are inserted under the tongue, the medicine is quick or
directly absorbed through the mucosal lining of the mouth beneath the tongue,
producing an instant systemic action.
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DRUGS FOR SUBLINGUAL ADMINISTRATION
 Dose less than 20 mg are suitable for sublingual drug delivery system.
 It has been a developing field in the administration of many vitamins and minerals
which are found to be readily absorbed by this method.
 Sublingually absorbed nutrition, which avoids exposure to the gastric system and liver,
means direct nutritional benefits, particularly important for sufferers of gastro-intestinal
difficulties such as ulcers, hyperactive gut, coeliac disease, those with compromised
digestion.
 Examples of drugs administered by this route include antianginal like nitrites and
nitrates, anti hypertensive like nifedipine, analgesics like morphine and bronchodilators
like fenoterol.
 Certain steroids like estradiol and peptides like oxytocin can also be administered e.g.
fentanyl
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 Sublingual tablet:
 Sublingual Tablets "Sublingual tablets are solid unit dosage form meant for
placement under the tongue to produce immediate action by avoiding the
first pass effect of drug by liver.“
 The tablets are usually small and flat, compressed lightly to keep them soft.
 The tablet must dissolve quickly allowing the API to be absorbed quickly. It
is designed to dissolve in small quantity of saliva.
 Swallowing of saliva should also be avoided since the saliva may contain
dissolved drug. Bland excipients are used to avoid salivary stimulation.
 Nitroglycerine tablets and Ondansetron tablets are the examples of
sublingual tablets.
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Mechanism of sublingual absorption:
Sublingual administration drug solutes are rapidly absorbed into the reticulated vein,
which lies underneath the oral mucosa and transported through the facial veins, internal
jugular vein and are then drained into the systemic circulation.
Upon sublingual administration drug reaches directly into the blood stream through the
ventral surface of the tongue and floor of the mouth.
The main mechanism for the absorption of the drug into oral mucosa is via passive
diffusion.
Sublingual formulation:
 Sublingual Tablets
 Sublingual Films
 Sublingual drops
 Sublingual spray
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FACTORS AFFECTING THE SUBLINGUAL ABSORPTION:
Solubility in salivary secretion:
In addition to high lipid solubility, the drug should be soluble in aqueous buccal fluids i.e. biphasic solubility of drug is necessary for
absorption.

Binding to the oral mucosa:

systemic availability of drugs that bind to oral mucosa is poor.

pH and pKa of the saliva:

As the mean pH of the saliva is 6.0, this pH favors the absorption of drugs which remain unionized. Also, the absorption of the drugs through
the oral mucosa occurs if the pKa is greater than 2 for an acid and less than 10 for a base.

Lipophilicity of the drug:

For a drug to be absorbed completely through sublingual route, the drug must have slightly higher lipid solubility than that required for GI
absorption is necessary for the passive permeation.

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ADVANTAGE
-Drug absorption is quick
-Quick termination
-First-pass avoided.
-Can be self administered drug
-Economical

DISADVANTAGES
-Unpalatable & bitter drugs
-Irritation of oral mucosal
-Large quantities not given
-Few drugs are absorbed
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 Table: Physicochemical Criteria of drug for Sublingual Drug Delivery

Physicochemical Properties Accepted Range

of Drug

Dose < 20 mg

Taste Not intensely bitter

Stability Good stability in water & saliva
Molecular weight Small to moderate (163.3-342.3g/mol)
pKa >2 for acidic Drug; < 10 for basic Drug

Log p 1.6 to 3.3

Lipophilicity Lipophilic

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 Aim:

Difficulty in swallowing (dysphagia) is a common problem of all age groups, especially the elderly and
pediatrics, because of physiological changes associated with these groups.
Aim of the work:
In the present work an attempt will be made to formulate nimodipine sublingual tablets, using different
super disintegrants for treatment of hypertension, the fast dissolving tablet provides a rapid onset of
action.
objectives of the work:
1. To design the formula for sublingual tablet.
2. To selected model drug and develop formula and prepare tablets.
3. To evaluate the formulated tablets.
4. To study the in-vitro dissolution profile of prepared tablets.
5. To carry out stability studies of the selected formulations
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 Need of work:
 Medications that are administered sublingually dissolve under the tongue, without chewing
or swallowing.
 Absorption is very quick, and higher drug levels are achieved in the bloodstream by
sublingual routes than by oral routes because-
(1) the sublingual route avoids first-pass metabolism by the liver

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 Plan of work :
Literature of Selection of
Selection of drug
review excipient

Post-compression
parameters:
Preformulation study
 Appearance  Selection of drug
Pre-compression
 Dimension  Organoleptic
parameters:
 Weight variation test Characteristics
 Hardness test  Angle of Repose Solubility Study
 Friability test  Bulk density  Determination of
 In-Vitro Dispersion Time Melting Point
 Tapped density Hausners
 Spectroscopic
 Disintegration time ratio
determination FTIR
 In-vitro dissolution  Compressibility index(%) Spectroscopy.
studies Compatibility study -By
 Compatibility Studies DSC 12
 Agheranikunj Jamnadas et al. (2012) Oral mucosal drug delivery is an alternative method of
Literature review

systemic drug delivery that offers several advantages over both injectable and enteral methods.
Because the oral mucosa is highly vascularized, drugs that are absorbed through the oral mucosa
directly enter the systemic circulation, bypassing the gastrointestinal tract and first-pass
metabolism in the liver. For some drugs, this outcome in rapid onset of action via a more easy and
convenient delivery route than the intravenous site. How ever, can be administered through the oral
mucosa because of the characteristics of the oral mucosa and the physicochemical properties of the
drug.
 Amit Kumar Bind et al. (2013) Drug delivery via the oral mucous membrane is considered to be a
promising alternative to the oral route. Sublingual route is a rapid onset of action and better patient
compliance than orally ingested tablets. Sublingual literally meaning is “under the tongue”,
administrating substance via mouth in such a way that the substance is rapidly absorbed via blood
vessels under tongue. The portion of drug absorbed through the sublingual blood vessels bypasses
the hepatic first‐pass metabolic processes giving acceptable bioavailability. Different techniques
are used to formulate the sublingual dosage forms

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 N.Nishan et al. (2013) Bioadhesion can be defined as a phenomenon of interfacial molecular
attractive forces in the midst of the surfaces of biological substrate and the natural or
synthetic polymers, which allows the polymer to adhere to biological surface for an extended
period of time. The buccal region is an offers adorable route of administration drugs for
systemic delivery. Among the various transmucosal sites available, mucosa of the buccal
cavity was found to be the most convenient and easily approachable site for the delivery of
therapeutic agents for both local and systemic delivery retentive dosage form. Because
buccal drug delivery system prolong the residence time of dosage form at the site.
 K.patel Nibha et al. (2012) Oral mucosal drug delivery is an alternative and promising
method of systemic drug delivery which offers several advantages. Sublingual literally
meaning is ''under the tongue'', administrating substance via mouth in such a way that the
substance is rapidly absorbed via blood vessels under tongue. Sublingual route offers
advantages such as bypasses hepatic first pass metabolic route which gives better
bioavailability, quick onset of action, patient fulfillment, self-medicated. Dysphasia
(difficulty in swallowing) is common between in all ages of people and more in pediatric,
geriatric, psychiatric patients. Sublingual area of oral cavity is more permeable compare to
buccal and palatal area
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 Formulation:

API (main drug ) Excipients

(active pharmaceutical drug) 1. Binders:- Lactose, Starch, Microcrystalline cellulose

2. Super disintegrants:- Sodium starch glycolate,
cross carmellose sodium
3. Lubricant:- Magnesium stearate or stearic acid
4. Glidant:- Talc, Magnesium carbonate
5. Polymer:- Hydroxypropyl Methylcellulose

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 EVALUATION TESTS
1)Uniformity of Weight:-
I.P. procedure for uniformity of weight was followed, twenty tablets were taken and their weight was
determined individually and collectively on a digital weighing balance. The average weight of one
tablet was determined from the collective weight.
Table 1: IP limit for weight variation

2)Friability:-
The friability of a sample of 20 tablets was measured using a Roche friabilator (Electrolab). 20
previously weighed tablets were rotated at 25 rpm for 4 min. The weight loss of the tablets before and
after¹
%Friability = Initial weight - final weight x 100
Initial weight
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 3)Tablet
Hardness:-
Hardness of tablet is defined as the force applied across the diameter of the tablet in the order to break the tablet. The
resistance of the tablet to chipping, abrasion or breakage under condition of storage transformation and handling before
usage depends on its hardness. Hardness of the tablet of each formulation was determined using Monsanto Hardness tester.

4)In-vitro dispersion time:-

can be measured by dropping a tablet in a beaker containing 50 ml of Sorenson's buffer pH 6.8.
invitro dispersion time is expressed in seconds.

5)Disintegration test:-
The test can be carry out on 6 tablets using the apparatus specified in LP. 1996 distilled water at 37°C 2°C was used as a
disintegration media and the time in second taken for complete disintegration of the tablet with no palable mass remaining
in the apparatus measure in seconds.

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6)Wetting Time:-
Using this test, the time required for moisture to penetrate the tablet completely is measured and
possibly represents the time required to release drug in the presence of minute volumes of saliva.
A piece of tissue paper (12 cm X 10.75 cm) folded twice was placed in a small Petri dish (ID = 6.5
cm) containing 6 ml of Sorenson's buffer pH 6.8. A tablet was put on the paper, and the time for
complete wetting was measured

7)Size and Shape:-

The size and shape of the tablet can be dimensionally described, monitored and controlled.

8)Tablet thickness:-
It is important characteristic in Tablet Thickness reproducing appearance and also in counting by
using filling equipment. Some filling equipment utilizes the uniform thickness of the tablets as
accounting mechanism. Tablet thickness can be measured by micrometer or by other device.
Tablet thickness should be controlled within a ± 5% variation of standard value.

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 Hypothesis:
 Sublingual products were developed to overcome the difficulty in swallowing
conventional tablet, among pediatric, geriatric and psychiatric patients with dysphagia.
 The potential for such dosage forms is promising because strong market acceptance
and patient demand.
 Peak blood levels of most products administered sublingually are achieved within few
minutes, which is generally much faster than when those same drugs are ingested orally.
Sublingual absorption is efficient.
 Sublingual tablets promote rapid absorption and higher bioavailability with an almost
instant onset of action
 Sublingual tablets can be used to achieve a rapid onset of action, better patient
compliance and increased bioavailability.

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Reference
1) Nikunj J. Aghera, Suresh D. Shah, Kantilal R. Vadalia Formulation and evaluation
of sublingual tablets of losartan potassium Asian Pacific Journal of Tropical
Disease (2012)S130-S135.

2) Amitkumar bind, g. gnanarajan and preetikothiyala review on sublingual route for

systemic drug delivery international journal of drug research and technology 2013,
vol. 3 (2), 31-36.

3) Nishan n. bobade , sandeep c. atram, vikrant p. wankhade, dr. s.d.pande, dr.

k.k.tapar a review on buccal drug delivery system international journal of
pharmacy and pharmaceutical science research 2013; 3(1): 35-40.

4) K.Patel Nibha1 and SS. Pancholi An Overview on: Sublingual Route for Systemic
Drug Delivery International Journal of Research in Pharmaceutical and
Biomedical Sciences ISSN: 2229-3701,2012.

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