FORMULATION DEVELOPMENT AND EVALUATION OF ANTI-TB TABLETS

Name of student Name of guide Mr.Vaibhav Tate Mrs.Swapnila Shinde (M. Pharm Sem – 3rd Pharmaceutics) (Dept. of Pharmaceutics)

Sinhgad Institute of Pharmacy, Narhe, Pune

CONTENTS

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INTRODUCTION

LITRATURE SURVEY

AIM & OBJECTIVE

PLAN OF WORK

EXPERIMENTAL METHODLOGY

EVALUATION

REFERENCE

INTRODUCTION

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Tuberculosis, or TB, is an infectious bacterial disease caused by Mycobacterium tuberculosis,

most commonly affects the lungs. It is transmitted from person to person via droplets from the throat and lungs of people with the active respiratory disease

gram +ve bacilliNon motile, non sporing,& noncapsulated

TRANSMISSIONTB spread from person to person by airborne

transmission. Infected person release droplet nuclei (1-5 micro meter in diameter) through, Talking Coughing Sneezing Laughing Singing

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SYMPTOMS

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SIGNIFICANT LAB TEST

Sputum examination and Cultures; Is examined under a microscope to look for tuberculosis bacteria and

used to grow the bacteria in a culture Interferon-gamma Blood test; A simple blood is mixed with synthetic proteins similar to those

produced by the tuberculosis bacteria. If people are infected with tuberculosis bacteria, their white blood

cells produce certain substances (interferon) in response to the synthetic proteins.

Imaging Consideration Chest C.T Scan Chest X Ray

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TREATMENT

• Prevent death

• Cure

• Prevent relapse

• Prevent transmission

• Prevent development of • Drug resistance

AIM

CLASSIFICATION OF DRUG

First-line drugs: good efficacy, less toxicity and being well tolerated for patients Isoniazid (INH), Rifampin, Pyrazinamide, Ethambutol, Streptomycin. Second-line drugs: usually used as alternatives to the first-line drug when drug

resistance occurs or when a particular therapy is required. Para-aminosalicylic acid, Kanamycin, Amikacin, Capreomycin, Ciprofloxacin, Ethionamide

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Trade name Active drug Manufacturer

3FD Isoniazide Novartis Pharmaceutical

Acute Z IsoniazideRifampicin Biocin Pharma

AKT 3 IsoniazideRifampicinEthambutol

Lupin Pharma

Afarcin 5IsoniazideRifampicin Assam Chemical &

Pharmaceutical Pvt Ltd

AFB 4 Isoniazide Lark Lab.

List of commercially Available AntiTB Tablets

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LITERATURE SURVEY

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LITERATURE SURVEY

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AIM AND OBJECTIVE

AIM : Formulation development and evaluation of Anti-TB tablet.

OBJECTIVE :1) To design, develop and evaluate oral tablet dosage form.2) To provide rapid disintegration ,systemic effect3) Rapid drug release4) To prepare stable formulation.

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PLAN OF WORK

• 1st – 2nd month

• Literature survey, selection of drug & excipients

• 3rd – 4th month

• Pre-formulation study & analytical method development

• 5th – 7th month

• Formulation , Development and Optimization

• 8th -10th month

• In- vitro & In-vivo Evaluation &Stability study as per ICH guidelines

• 11th -12th month

• Thesis writing & Publication

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TB Drug Selection

Bio-equivalence /Bio-availability Drug formulations (tablets, fixed-dose combination tablets

soluble tablets, powder in sachets) Marketing approval/registration Applied pharmacy-economics:

the most cost effective TB treatment = DOTS Costs of different drugs, availability, delivery times

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DRUG PROFILE

ISONIAZIDE

Appearance: White Crystalline Powder

Mol wt : 137.14

Structure:

IUPAC name: pyridine-4-carbohydrazide

Empirical formula: C6H7N3O

Melting point: 170-173 oC

Solubility : soluble In water

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Isoniazide It is the most active drug for the treatment of tuberculosis

After orally administered, well absorbed, widely distributed in body.

Most INH is metabolized in the liver

Mechanism of action

the inhibition of synthesis of mycolic acids, which are important and

characteristic components of mycobacterium cell wall.

As a result of the activity, tubercle bacilli lose their features of acid-

resistance, water-resistance and proliferating ability, leading to death.

Pharmacologic activity- It is bactericidal for actively growing tubercle bacilli. But, for resting

tubercle bacilli, it is bacteriostatic. Isoniazid is able to penetrate into phagocytic cells and thus is active

against both extracellular and intracellular organisms.

Adverse Reaction Allergic Reaction: fever, skin rash. Nausea Vomiting Weakness Dark Urine

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SELECTION OF EXCIPIENTS

Excipients are selected on the basis of compatibility and release of drug from formulation

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FORMULATION AND DEVELOPMENT OF TABLETS

EXCIPIENTS EXAMPLES

API ISONIAZIDE

Binders Maize starch.

Disintegrates Carmalose sodium

Wetting Agent Sodium Lauryl Sulphate

Lubricants Talc, Ca-stearate

solvent Purified water

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TECHNIQUES USE TO PREPARE TABLETS

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PREFORMULATION STUDY

Preformulation Parameter

Affected Properties Evaluation Technique

Color Purity Color strips

Odor Purity Inhalation

Melting point Purity Melting point apparatusDetect Physical changes

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PREFORMULATION STUDY

Preformulation Study Affected Properties Evaluation techniqueParticle Size Distribution

Flow properties during filling, reconstitution time, blend uniformity,syringeability

Sieve analysis with particle sizing equipment

Bulk density & compactability

Flow properties and compact formation in dry powders for reconstitution

Angle of repose, Carrs’ Index, Hausner ratio

Charactrization Provides additional information about drug I.R

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PREFORMULATION STUDY

Characterization of Drug

• Melting Point Determination

Apparatus- Buchi-M560

Standard M.P-170-173 oC

Observed M.P 173 oC

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PREFORMULATION STUDY

FT-IR Spectroscopy of Isoniazide:Apparatus-Perkinelmer 304082

Software-Spectraes

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EVALUATION TABLETS

• General parameters

• Hardness

• Friability

• Weight variation

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EVALUATION OF TABLETS

• Disintegration time

• Content uniformity

• Dissolution test

Stability

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Approach to understanding the mechanism of action of isoniazid, an anti-TB Drug Lingaraja Jena a, Pranita Waghmare a, Supriya Kashikar b, Satish Kumar Received 2 August 2014 Accepted 5 August 2014 Available online 2 September 2014

Quality Problem of Anti-TB FDC Combination a way to Forward Saranji Singh1, Hemant Bhutani2 and T.T. Mariappan3 (Original receive on 13.12.2005. Revised version received on 6.3.2006. Accepted on 6.6.2006)

REFERENCE

. Treatment of tuberculosis. In: Sharma SK, Mohan A (Eds). Tuberculosis, 2nd edn. New Delhi: Jaypee Brothers Medical Publishers; 2009.pp.751-75.

Centers for Disease Control and Prevention Division of Tuberculosis Elimination website http://www.cdc.gov/nchstp/tb

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REFERENCE

Handbook of Anti-Tuberculosis Agents Global Alliance for TB Drug Development 80 Broad Street Volume 88 Number 2 2008 Pages 85–170

Effect of maize starch excipient properties on drug release Rate P. Zámostný a*, J. Petrů, D. Majerová a Department of Organic Technology, Faculty of Chemical Technology, Institute of Chemical Tech Prague Technika 5, 166 28

http://www.who.int/tb/en/

http://www.drugbank.ca/drugs/DB00951