FORMULATION, EVALUATION AND OPTIMIZATION OF AZITHROMYCIN ORALLY

DISSOLVING FILMPrepared by GARGI DAS

M.PHARM (PHARMACEUTICS)Roll No. – 19320314003

Registration No. - 141932310009Under the supervision of Mr. KH. HUSSAN REZA

(Assistant Professor)Bengal School of Technology

FLOW OF CONTENTSIntroductionObjective and purposeLiterature reviewsProposed plan of workProbable materials to be used for formulationDrug profileFormulation processWork done so farReferences

INTRODUCTION Oral dissolving film is solid dosage form which

is thin polymeric strip incorporating and delivering pharmaceutical active ingredients & once placed in the mouth dissolves in a short period of time without drinking water or chewing.

These are also called as:- Oral thin films Mouth dissolving films/strips. Buccal films/strips. Fast dissolving films. Oral strips.

Benefits of ODF: Quick onset of action and enhance efficacy.

Avoidance / reduction of first pass metabolism.

Improve patient compliance. Pain free administration.

No need of water.

Films can be produced easily by industrially feasible and scalable methods.

Limitation Of ODF: Drugs which are unstable at buccal pH cannot

be administered.

Drugs which irritate the mucosa cannot be administered by this route.

Drug with small dose requirement can only be administered.

Special packaging method needed.

OBJECTIVE AND PURPOSES The present study is an attempt to develop an

alternative dosage form for the existing conventional system as Oral Dissolving Film (ODF) of Azithromycin for treating infants (1-2 years).

In the present work an attempt is made to formulate a ODF of Azithromycin that can immediately dissolve in the oral cavity (30 second approximate) releasing the drug that can reach to the systemic circulation via oral blood vessels, resulting in a rapid onset of action by passing or reducing first pass metabolism.

The Azithromycin ODF is planned to be prepared by using various polymer grades within a planned statistical framework of Design of Experiment that will help in product development and optimization. Therefore, present work is aimed to formulate and evaluate ODF by combining different polymer grades to study the effectiveness in drug release pattern.

LITERATURE REVIEW Dixit et al8, 2009 reviewed on Oral Strip Technology: Overview and future potential.

The review described about materials used in OST, critical manufacturing aspects, applications, commercial technologies and future business prospects of this technology.

  Patil et al1, 2012 reviewed on Fast Dissolving Oral Films: An Innovative Drug Delivery

System. The review described about the excipients required for formulation along with methodologies and evaluation parameters.

Ghodake et al9, 2013 reviewed on Mouth Dissolving Films: Innovative Vehicle for Oral Drug Delivery. This review provided an account of various formulation methods and their evaluation used in film formulation and applications of mouth dissolving film. The conclusion was that the oral route is most popular route for the administration of therapeutic agents as mouth dissolving film.

  Harber et al10, 2014 worked on Orally Administrable Films and Preparation thereof.

The invention related to an orally administrable mucoadhesive film which comprises one or more bioactive ingredients and as a major film forming polymer at least one alginate which is capable of forming a low viscosity aqueous solution. Also provided a process for preparing such films.

PROPOSED PLAN OF WORK Preparation of calibration curve of

azithromycin dihydrate.  Preformulation Study –1. Identification tests of drug.2. Drug excipients interaction studies.  Formulation design – Formulation of ODF based on factorial design.  Evaluation tests .

PROBABLE MATERIALS TO BE USED FOR FORMULATIONTable 1: - List of materials to be used for

formulation.Name Rationality Source

Azithromycin Dihydrate Active Pharmaceutical Ingredient

Standard Pharmaceutical Ltd.

Hydroxy Propyl Methyl Cellulose E15 and E15 Premium LV,,E3 Premium LV, E5 Premium LV, E6 Premium LV.

Polymers, Film forming agent

Loba Chemie.

Poly Vinyl Alcohol Polymer, Film forming Agent.

sd fine chem ltd.

Poly Ethylene Glycol 400 Plasticizer Merck Specialities Private Ltd.

Glycerol Plasticizer Fisher Scientific

Menthol Flavoring agent B.S. Trading

Eucalyptol Flavoring agent B.S. Trading

Aspartame Sweetener B.S. Trading

Acesulfame Potassium Sweetener sd fine chem. ltd.

Citric Acid Salivary stimulating agent sd fine chem. ltd.

DRUG PROFILEDrug: - Azithromycin Dihydrate.

Physicochemical Properties :- Molecular weight: - 785.02g/mol. Molecular formula: - C38H72N2O12. 2H 2O. Log P :- 4.02 pKa :- 8.74 (at 25°C) Melting point :- 114°C Solubility: - Soluble in ethanol and methanol.

DRUG PROFILEPharmacokinetic Properties: -

Biological half life: - 11-14 hours. Protein binding: - Serum protein binding is variable in

the concentration range approximately human exposure, decreasing from 51% at 0.02 µg/ml to 7% at 2µg/ml.

Pharmacological and Clinical Activity :- Azithromycin, a semi synthetic antibiotic

belonging to the macrolide subgroup of azalides, is used to treat community acquired pneumonia, pelvic inflammatory disease, pediatrics otitis media and pharyngitis, and Mycobacterium avium complex (MAC) in patients with HIV disease.

 

DRUG PROFILE

FORMULATION PROCESS Solvent casting.

Rolling.

Hot melt extrusion.

Semisolid casting.

FIG. 1 : -Solvent casting apparatus

FIG. 2 : - The manufacturing techniques for oral thin films, 1- Polymer mixing, 2- Layering and mother roll formation, 3- Slitting of mother roll, 4&5- packaging.

Work done so far….Table 2: - Identification Tests (I.P)

Tests Procedure Result

Appearance of solution:- 0.5g of drug (azithromycin dihydrate) was dissolved in anhydrous ethanol & diluted to 50.0ml with the same solvent. The solution should be clear and colorless.

Solution was clear and colorless.

pH:- A solution was prepared by dissolving 0.1g of drug in 25.0ml of methanol and further diluting to 50.0ml with carbon dioxide free water. The pH should be 9.00-11.00.

9.83.

Infrared Spectroscopy:-

As per method. The peaks were matched with reference peaks of drug.

Complied

FIG. 3:- IR Spectrum of Azithromycin dihydrate (Standard drug).

FIG. 4: - IR Spectrum of Azithromycin dihydrate.

REFERENCES1. Patil S L, Mahaparale P L, Tiwari S S, Pavour K V, Sane P N. Fast Dissolving Oral Films: An

Innovative Drug Delivery System. International Journal of Research and Reviews in Pharmacy and Applied Science.2012; 2(3): 482-496.

2. Thakur N, Bansal M, Sharma N, Yadav G, Khare P. Overview “A Novel Approach of Fast Dissolving Films and Their Patients”. Advances in Biological Research. 2013; 7(2): 50-58.

3. Sloboda M, Barnhart S. Formulation Flexibility Broadens The Scope For Oral Thin Film Technology. Adhesives Research. 2011; 22-24.

4. Bansal S, Bansal M, Garg G. Formulation And Evaluation of Fast Dissolving Film of an Antihypertensive Drug. International Journal of Pharmaceutical Chemical And Biological Sciences. 2013; 3(4): 1097-1108.

5. Aggarwal J, Singh G, Saini S, Rana A C. Fast Dissolving Films: A Novel Approach to Oral Drug Delivery. International Research Journal of Pharmacy. 2011; 2(12): 69-71.

6. Radhakisan U R, Chavan V, Tribhuvan N. Mouth Dissolving Film and Their Patent: An Overview. International Research Journal of Pharmacy. 2012; 3(9): 39-42.

7. Arya A, Chandra A, Sharma V, Pathak K. Fast Dissolving Oral Films: An Innovative Drug Delivery System and Dosage Form. International journal of Chem Tech Research. 2010; 2(1): 576-583.

8. Dixit R P, Pahli S P. Oral Strip Technology: Overview and future potential. Journal of Controlled Release. 2009; 139: 94-107.

9. Ghodake P P, Karande K M, Osmani R A, Bhosale R R, Harkare B R, Kale B B. Mouth Dissolving Films: Innovative Vehicle for Oral Drug Delivery. International Journal of Pharma Research & Review. 2013; 2(10): 41-47.

10. Harber Meir. Orally Administrable Films and Preparation Thereof. US; US8,840,935 B2, 2014.