Formulation and Evaluation of Mucoadhesive Buccal Patches of Theophylline

Formulation and Evaluation of Mucoadhesive Buccal Patches of Theophylline

FORMULATION AND EVALUATION OF MUCOADHESIVE BUCCAL PATCHES OF THEOPHYLLINE

M. Pharm. Dissertation Protocol

Submitted to

RAJIVGANDHIUNIVERSITY OF HEALTH SCIENCES,BANGALORE,

KARNATAKA

By

Mr. SRINIVAS R. DIWANB.Pharm

Under the guidance of

Dr. ANITA R. DESAIM.Pharm., PhD.

Asso. Professor

DEPARTMENT OFPHARMACEUTICS

H.S.K. COLLEGE PHARMACY

BAGALKOT-587 101

(2012-13)

ANNEXURE II

PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION

1 / Name of the Candidate and Address / SRINIVAS R. DIWAN
H.S.KCOLLEGE OF PHARMACY
B.V.V.S CAMPUS
BAGALKOT-587101
PERMANENT ADDRESS
SHRINIVAS R. DIWAN
S/O R.D.K.DIWAN
At:Post- Hirebendigeri
Tq-shiggaon.Dist-Haveri
Pin-581205
KARNATAKA.
2 / Name of the Institution / H.S.KCOLLEGE OF PHARMACY
H.S.KCOLLEGE OF PHARMACY
B.V.V.S CAMPUS
BAGALKOT-587101
3 / Course of the Study and Subject / M. PHARMACY
(PHARMACEUTICS)
4 / Date of Admission / 30-07-2012
5 / Title of the project:- “FORMULATION AND EVALUATION OF MUCOADHESIVE BUCCAL PATCHES OF THEOPHYLLINE”
6.0
7.0
8.0 / BRIEF RESUME OF THE INTENDED WORK:
6.1 Need for the study:
Bioadhessive formulations have wide scope of applications, for both systemic and local effects of drugs. The mucosa is relatively permeable with a rich blood supply. The oral transmucosal drug delivery bypasses liver and avoids pre-systemic elimination in the GI tract1 and liver2. These factors make the oral mucosa a very attractive and feasible site for systemic drug delivery and bioavailability problems3
Bronchial asthma is a disease of airways that is characterized by increased responsiveness of the tracheobronchial tree to a variety of stimuli resulting in widespread spasmodic narrowing of the air passages which may be relieved spontaneously or by therapy.4According to the Global Burden of Asthma Report asthma is one of the world’s most common long-term conditions and is estimated to affect as many as 300 million people worldwide, that could increase by a further 100 million by 2025. It has been reported that over 50 million people suffer from Asthma in central and southern Asia and is predicted to increase rapidly in the coming years. The increase is likely to be particularly dramatic in India. An absolute 2% increase in the prevalence of asthma in India would result in an additional 20 million people with the disease.5
Theophylline, also known as dimethylxanthine, is a methylxanthine drug used in therapy for respiratory diseases such as COPD or bronchial asthma.21Anti-inflammatory drugs have become mainstay for asthma prophylaxis. But theophylline is found to be exerting anti inflammatory effect even at serum concentration below the accepted therapeutic range. Theophylline also attenuates the asthmatic reaction to inhaled allergens.6,7
In the treatment of nocturnal asthma a controlled release formulation is most preferred since they avoid intermittent dosing. Due to its low therapeutic index, gastrointestinal toxicity starts from the upper therapeutic range.8 The porous osmotic pump of theophylline can provide a better therapeutic efficiency along with reduced side effects by a precise and controlled release of the drug.
The present study will be carried out with an attempt to develop mucoadhesive buccal drug delivery system of salbutamol sulphate. The buccal mucoadhesive film of salbutamol sulphate will be prepared either by solvent casting technique or titration method of drug polymer ratio using various polymers like HPMC, HPMCP, Chitosan, Carbopol-934, Eudragit, PVP and EC.
6.2 Review of Literature:
Thimmasetty J et al., (2008) Studied on design and invivo evaluation of carvedilol buccal mucoadhesive patches by using HPMC, Carbopol 934, Eudragit RS 100 and Ethyl cellulose. Patches exhibited drug release in the range of 86.26 to 98.32% in 90 min. invivo studies in rabbits showed 90.85% of drug release from HPMC – Carbopol patch while it was 74.63 to 88.02% within 90 min in human volunteers. Good correlation among invitro release and invivo release of carvedilol was observed2.
Pavankumar GV et al., (2005) Studied on formulation of buccal films of salbutamol sulphate by using HPMC 50 CPS, Ethyl cellulose and Eudrajit RL 100. The physico – chemical parameters like thickness, density, folding endurance, swelling index,and mucoadhesive strength based on shear stress and tensile strength, water permeability, drug content and drug release characteristics were evaluated. The drug release studies indicated the first order controlled release kinetics in all cases. It was also observed that the lower the permeability co – efficient the greater was the extended release characteristics for buccal films. Finally it was concluded that the polymers and their combination influenced the film properties as well as release characteristics10.
Satishbabu BK et al., (2008) Studied on bioadhesive films of atenolol by using bioadhesive polymer Sodium alginate with or without carbopol 934 p and backing layer was made of ethyl cellulose. It exhibited well-controlled and delayed release pattern. This study concludes that, the addition of carbopol 934 p increases the viscosity and swelling of films there by controls the release of drug and improves the mucoadhesive properties11.
Vamsi Vishnu Y et al., (2007) Studied on mucoadhesive patches for buccal administration of carvedilol by using HPMC E15, HPC JF. Good results were obtained both invivo and invitro condition for films of HPMC E 15 LV. The bioavailability of carvedilol increased by about 2.29 times. Bioadhesive buccal formulation for carvedilol may be a promising one as the dose of carvedilol may be decreased and hence side effects may be reduced12.
Doijad RC et al., (2008) Studied on buccoadhesive drug delivery system of isosorbide dinitrate film by using two different plasticizers Propylene glycol and Diethylpthlate. Drug diffusion from bucccal films showed apparently zero order kinetics and release mechanism was diffusion controlled after considerable swelling. All the films exhibited sufficient invitro bioadhesive strenth13.
Khanna R et al., (1997) Studied on preparation and evaluation of mucoadhesive buccal films of clotrimazole for oral Candida infections by using carbopol 934 P (CP -934 P), Hydroxy propyl cellulose –M (HPC –M), HPMC –E4M, Eudragit –RLPM (EU –RLPM) and Eudragit –NE 30D (EU –NE 30D). The film exhibited an invitro adhesion time of 4 hours and maintained the concentration of clotrimazole in dissolution medium above the MIC of Candida albicans for upto 4 hours. The drug release from the formulation was found to be microbiologically active14.
Ilango R et al., (1997) Studied on invitro studies on buccal strips of glibenclamide by using Chitosan, Eudragit L 100, Eudragit S 100, Polyvinyl pyrrolidone (kollidone), Propylene glycol obtained a slow release, relatively constant effective levels of glibenclamide from buccal strips using chitosan. Invitro studies in chitosan matrix showed that the percent release was 80.5%, with eudragit buccal strips showed that the percent release was 78%. The greater swelling nature of chitosan may perhaps be responsible for the promising diffusion controlled drug release than the eudragit based system15.
Nafee NA et al., (2003) Studied on design and characterization of mucoadhesive buccal patches containing Cetylpyridinium chloride by using Poly vinyl alcohol (PVA), Hydroxy ethyl cellulose (HEC) and Chitosan. The physical characteristics of the studied patches showed an increase in the residence time with storage accompanied with a decrease in drug release. This may be due to changes in the crystal habit of the drug as well as to slight agglomeration of the polymer particles16.
Vinod R et al.,(2010)The study was to formulate and evaluate buccal patches containing an antifungal agent (Miconazole nitrate), using different ratio of HPMC E 50, Carbopol,Ethyl cellulose, in order to obtain new formulation. The patches were prepared by solvent casting method and characterized by folding endurance, patch thickness, drug content, surface pH, bioadhesive time, tensile strength, swelling study, invitro drug release and exvivo diffusionprofile. All the formulations gave the satisfactory results in terms of physical and mechanical properties and surface pH. Drug release and drug diffusion fromthe patches were depended on the ratio and type of the polymer used in the formulation. The best mucoadhesive performance and best invitro drug releaseprofile were achieved in formulation F2 containing drug: HPMC E 50: Carbopol (1:1)17.
6.3 Objectives of the study :
The present work was planned with the following objectives
  1. Preparation of mucoadhesive buccal film of Theophylline using various polymers like HPMC,HPMCP,Carbopol, Chitosan, EC, MC, Gelatin and PVP etc.
  2. Formulation studies of mucoadhesive buccal film of Theophylline.
  3. Evaluation studies of the influence of drug carrier ratio and drug release studies.
  4. Evaluation includes determination of size, shape, tensile strength, swelling properties, drug content and invitro drug release studies of Theophylline.
Materials and Methods :
7.1 Drugs to be used in the formulations:
Drug : Theophylline.
Polymer : Hydroxy propyl methyl cellulose, Eudragit, Carbopol, Ethyl cellulose,
Poly vinyl Pyrrolidone, Sodium methylcelluloseChitosan etc.
Method : Development of mucoadhesive patches by solvent casting technique.
7.2-Source of Data:
Review of Literature from
a)Journals such as
  1. Indian Journal of Pharmaceutical Sciences.
  2. Indian Drugs.
  3. Journal of Controlled Release.
  4. International Journal of Pharmaceutics.
  5. Pakistan Journal of Pharmaceutical Sciences.
  1. Drug Development and Industrial Pharmacy.
  2. Acta Pharma.
b)world wide web.
c)J–Gate@helinet.
d)Library :H.S.KCollege of Pharmacy.
7.3-Method of collection of data:
1)Preformulation studies for possible drug/polymer interactions by IR/DSC analysis.
2)Preparation of mucoadhesive patches by solvent casting technique.
3)Evaluation of various properties of mucoadhesive patches.
a)Film weight and thickness
b)Surface pH of the film
c)Percentage swelling
d)Bioadhesive strength
e)Folding endurance
4)Release study using suitable invitro model.
5)Exvivo permeation studies.
6)To carry out short term stability studies.
7.4Does the study require any investigations or interventions to be conducted on patients or other humans or animals? If so, Please describe briefly.
-----Not applicable-----
7.5 Has ethical clearance been obtained from your Institution in case of 7.3?
-----Not applicable-----
List of References :
  1. Pandey S,Pai M,Singh UV, Udupa N. Mucoadhesive formulations of theophylline Ind J Pharm Sci 1998;241.
  2. Thimmashetty J, Pandey GS,Satishbabu PR.Design and invitro evaluation of carvedilol buccal mucoadhesive patches Pak J Pharm Sci 2008; 21(3):241-248.
  3. Alka G, Sanjay G, Roop KK.Measurement of bioadhesive strength of mucoadhesive buccal tablets Indian drugs 1993.
  4. World Asthama Day 2004 regional press release, central and southern Asia. 2004 May 4.
  5. Theophylline. [online]. Available from: URL:
  6. Daga SR,Verma B, Mhapankar A,Kulkarni S, Kamble P. Theophylline in chronic asthma: A “before and after” study. The Internet Journal of Pediatrics and Neonatology2008;8(1).
  7. Barnes PJ, Pauwels RA. Theophylline in the management of asthma: time for reappraisal? Eur Respir J 1994;7:579–91.
  8. Tripathi KD. Essentials of medical pharmacology. 5th ed. New Delhi: Jaypee brothers medical publishers (p) ltd; 2003. p. 201-203.
  9. Satoskar RS, Bhandarkar SP, Nirmal NR.Pharmacology and Pharmacotherapeutics, 19th edition 2005; 354-357. World Asthma Day 2004 regional press release: central and southern Asia. 2004 May 4.
  10. Pavankumar GV, Ramkrishna V, William JK.Formulation and evaluation of buccal films of salbutamol sulphateInd J Pharma Sci 2005; 2:160-164.
  11. Satishbabu BK, Srinivasan BP. Preparation and evaluation of buccoadhesive films of atenolol Ind J Pharm Sci 2008; 70(2):175-79.
  12. Vamshi VY, Chandrasekhar K, Ramesh G, Madhusudanrao Y. Development of mucoadhesive patches for buccal administration of carvedilol Current drug delivery 2007; 4: 27-39.
  1. Doijad RC, Manvi FV, Malleswara RV, Patel PS. Buccal drug delivery system of isosorbide dinitrite formulation and evaluation Ind J Pharm Sci 2008; 68(6): 744-48.
  2. Khanna R, Agarwal SP, Alka A. Preparation and evaluation of muco-adhesive buccal films of clotrimazole for oral candida infections Ind J Pharm Sci 1997; 59(6): 299-305.
  3. Ilango R, Karimani S, MullaicharamAR, Jayakar B. In vitrostudies on buccal strips of glibenclamide using chitosan Ind J Pharm Sci 1997; 59(5): 232-35.
  4. Nafee NA, Nabila AB, Fatima MM. Design and characterization of mucoadhesive bucccal patches containing cetylpyridinium chloride Acta Pharm 2003; 53: 199-212.
  5. Vinod R, Ashok KP, Someshwara RB, Suresh VK and Shankar MS. Design and evaluation of miconazole nitrate buccal mucoadhesive patches J Pharm Sci 2010; 3(6), 1338-1341.
  6. Viral S, Manish P,Naresh R.Formulation and evaluation of pulsatile drug delivery of salbutamol sulphate Int J Pharm Sci Review and Research, 2010; 4 (3):59-63.
  7. Good Mann and Gillmans.The Pharmacological basis of Therapeutics 9th edition; 1786.
  8. PramodkumarTN, Kashappagoud D, Shivakumar HG.Mechanism of buccal permeation enhancers Ind J Pharm Edu 2002;36(3):147-151.
  9. Perioli L, Ambrogi D, Givvaquali S, Ricci M, Blasi P et-al.Novel mucoadhessive buccal formulation containing Metranidazole for the treatment of periodontal disease J Control release 2004;95:521-33.
  10. Ali J, Kha RK, Ahuja A, Kalra R.Buccoadhessive erodible risk for treatment of oral dental infections design and characterizations Int J Pharm Sci 2002; 238:93-103.
  11. ShinSC, Bum JP, Choi JS.Enhanced bioavailability by buccal administration of triamcindone acetamide from the bioadhesive gels in rabbits Int J Pharm Sci 2000; 209:37-43.
  12. SolomatMN, Chittchang M, Johnston TP.The use of mucoadhesive polymers in buccal drug delivery Advanced drug delivery Review, 2005; 57; 1666-91.

9 / Signature of the Candidate / (SRINIVAS R. DIWAN)
10 / Remarks of the Guide: / The topic selected for dissertation is satisfactory and feasible
11 / Name and Designation :
11.1. Guide: / Dr. ANITA R. DESAIM.Pharm., PhD.
HEAD OF THE DEPARTMENT OF
PHARMACEUTICS
H.S.K COLLEGE OF PHARMACY,
BAGALKOT-587101
11.2. Signature of Guide / (Dr. ANITA R. DESAI)
11.3. Co-Guide / NOT APPLICABLE
11.4. Signature of Co- Guide / NOT APPLICABLE
11.5. Head of the Department: / Dr. ANITA R. DESAIM.Pharm., PhD.
HEAD OF THE DEPARTMENT OF
PHARMACEUTICS
H.S.K COLLEGE OF PHARMACY,
BAGALKOT-587101
11.6. Signature of HOD / (Dr .ANITA R. DESAI)
12 / 12.1. Remarks of the principal / All the required facilities will be provided to carry out dissertation work under the supervision of the guide.
12.2. Principal / Dr. I. S. MUCHCHANDIM.Pharm., PhD.
PRINCIPAL
H.S.K COLLEGE OF PHARMACY
BAGALKOT-587101
12.3. Signature of the Principal / (Dr. I. S. MUCHCHANDI)