RESEARCH PROPOSAL DEFENSE PRESENTATION

SYSTEMATIC REVIEW ON INFANT ORAL FORMULATIONS FOR

COMMON MEDICAL ISSUES IN MALAYSIA
NARESH JAYABALAN
QIUP 201710-001528
INTRODUCTION
• Infants usually requires medicines that are specifically designed for
them due to differences in development in terms of physiology,
cognitive and motor skills compared to adults (Gerrard et al., 2019)
• Advantages that provided by oral liquid dosage forms that makes it
very popular among infants
• Facilitate the ease of swallowing which makes administering it easier (Gerrard
et al., 2019)
• Lack of commercially available oral liquid dosage forms for infants
leads to off label use of medicines for these group of patients
• There are several problems associated with off label use of products
I. Lack of access to various publications containing stability data on different drug
formulations (Pai and Nahata, 2001)
II. Lack of information about chemical, physical and microbiological stability data as well as
short shelf life (Brion et al., 2003) (Giam and McLachlan, 2010) (Pai and Nahata, 2001)
(Standing and Tuleu, 2005).
III. Carry risk of lack of proof of dose uniformity (Costello et al., 2007)
IV. Microbiological contamination in multidose off label preparations with insufficient
preservation leads to potential risks, especially in the premature and newborns (Ghulam et
al., 2007)
V. Adverse drug reactions are difficult to assess in off label preparations due to presence of
unknown excipients in commercially available preparations (Conroy S., 2008)
VI. Significant difference in bioavailability between specialized preparations for infants, off
label preparations, and manipulated medicines (Stevenson J., 2008).
BACKGROUND OF
STUDY
List of Common Symptoms Among Infants
for Various Disease Conditions
• Fever
1. Common Symptoms in Various Disease
Conditions
Medical Issue Explanation Reference
Fever Sign of mild or more serious illness and causes of (Purssell, 2010)
fever in infants include colds, flu, mumps,
chickenpox, urinary and kidney infections, measles
and teething
Concern to many parents and may indicate more (Van Den Bruel et al., 2006)
severe diseases such as bacterial infections like
meningitis, septicaemia and urinary tract infection
Most common complaint in paediatric emergency (Armon et al., 2001)
department, accounting nearly 20% of paediatric
emergency department visits
Symptoms Explanation Reference
Respiratory related Pneumonia-Becomes the cause for about 30-60% (Mitra NK., 2001)
Symptoms 0f hospital visits around the world as well as 20-
30% of hospital admission for children

Children with pneumonia were have chief (Shaheen et al., 2017)

complaints such as fever, cough, runny nose, and
sore throat and about 62.7% of paediatric patients
had more than one respiratory symptoms
Asthma-One of the chronic diseases in paediatrics (Kudzyte, J., Griska, E., & Bojarskas,
& it more prevalent among paediatrics compared J., 2008)
to adults (Ghaffari & Aarabi, 2013)
An increase in evidence that paediatrics are (Mahashur, 2015)
inappropriately treated for asthma based on
cough as the solitary symptom
Cough-Common medical problem in paediatric (Paramesh H., 2017)
patient and most common paediatric problem
managed by physicians
 2. Commonly Used Medicines for Infant
Class of Drug
Related
Drugs
Disease Symptoms
Reference
NSAIDS Paracetamol were most Venkateswaramurthy et al., 2017
commonly prescribed in Ithnin et al., 2018
hospitalized paediatric patients BOTZENHARDT et Al., 2016

Ibuprofen were second mostly BOTZENHARDT et Al., 2016

prescribed drug for paediatric Palanisamy et al., 2012
patients

Antibiotics Amoxicillin was the most Tea MH, 2016

commonly prescribed for
paediatric patients
Erythromycin was second
commonly prescribed antibiotic
for paediatric patients
Venkateswaramurthy et al., 2017
Shaheen et al., 2017
Ithnin et al., 2018
Meesala, 2017
Class of Drug Drug
Bronchodilators Salbutamol was the most
commonly prescribed among
paediatric patients
Antihistamines Diphenhydramine was the
most commonly prescribed for
children under age of 2
Chlorpheniramine also
commonly prescribed for
paediatric patients
Cetrizine was prescribed for
paediatric patients
Reference
Venkateswaramurthy et al.,
2017
Ithnin et al., 2018
Palanisamy et al., 2012
Pasupathi S., 2016
Mohamad et al., 2014
Pasupathi S., 2016
Palanisamy et al., 2012
Mohamad et al., 2014
Palanisamy et al., 2012
3. Infant Oral Formulations available
• Available in the form of ready-to-use or require manipulation and
multiuse or single use (Strickley, 2019)
• Ready-to-use formulations
• Oral solution, oral suspensions
• Formulations Require Manipulations
• Sprinkle capsule, powder for oral solution, powder for oral suspension,
granules for oral suspension, oral powder oral granules,
4. Excipients Used in Paediatric Oral
Formulations
• Functions of Excipients in pharmaceutical dosage forms
• Facilitate the manufacturing processes
• Improve the stability of the preparations during the storage as well as usage
(Burgess, 2017)
• To mask the taste of drug and improve its stability during storage period (Van Riet-
Nales et al., 2013)
• Excipients used in paediatrics drug formulations may bring potential harm to
infants.
• They not able to metabolize the excipients used in the formulations as adults due the
immaturity of their hepatic and renal system for metabolism and elimination
(Burgess, 2017)
• Use of preservative in paediatric formulations should be avoided and lowest
feasible concentration only should be used if needed (Oishi S.,2004)
5. Global Regulations & Guidelines for
Paediatric Drug Development
• In 2007, World Health Organization (WHO)
• Launched “make medicines child size” to increase awareness for more availability and
accessibility to child specific medicines
• Published guidance document in development of paediatric medicines which explains the
development aspects of paediatric medicines such as desirable features of dosage form,
flexible dosage form, formulation design, safe use of excipients and many others (Ch,
Rasekaran, K, & Asamy, 2018)
• In 2007, in Europe
• Paediatric regulation was implemented for the development of paediatric specific drug
products
• 10 year market exclusivity can be under Paediatric use Marketing Authorization (PUMA)
and 6 months of extension to Supplementary Protection Certificate (SPC) for paediatric
drug products upon approval of Paediatric Investigation Plan (PIP) in Europe (Walsh, 2017).
Problem Statement
• Lack of specialized formulations for infants has resulted in increased
use of off-label preparations, which maybe harmful to infants
• Infants have limited capacity to swallow oral liquid preparations
• Challenges to formulate concentrated low volume preparations using
solid dosage forms
• Excipients used in regular dosage forms might cause harm to infants
• Inconsistent efficacy, bioavailability, content uniformity and stability
Aim & Objective

Aim of the Study

• To study systemic review on commonly used infant medications in
Malaysia

Objectives of the Study

• To identify common medical issues among infants in Malaysia
• To identify management of common medical issues among infants in
Malaysia
• To identify pharmaceutical preparations for infants in Malaysia
Significance of Study

• Will provide insight on oral medication practices for common medical

issues for infants in Malaysia
• Will provide selection of suitable oral preparations for management
of common medical issues for infants in Malaysia
• The study will highlight the need for specialized oral medications for
infants in Malaysia
Research Methodology
• Identification of commonly prescribed drugs for infants for common
medical issues as per Ministry of Health, Malaysia official guidelines
• Prescribing information will be obtained from various official sources
from Ministry of Health, Malaysia and various research publications
• The availability of registered dosage forms of drugs used in infants will
be obtained from National Pharmaceutical Regulatory Agency (NPRA)
official website.
References