“FORMULATION DEVELOPMENT AND EVALUATION OF SERTRALINE HYDROCHLORIDE BUCCAL PATCHES.”
M. Pharm Dissertation Protocol Submitted to
Rajiv Gandhi University of Health Sciences, Karnataka
Bangalore– 560 041
By
Mr. Pankaj N. Patel B.Pharm.
Under the Guidance of
Mrs. S. Anitha M.Pharm. (Ph.D)
Asst. Professor.
Department of Pharmaceutics,
Acharya & B.M.Reddy College of Pharmacy,
#89/90, Soldevanahalli, Chikkabanavara (Post)
Hesaraghatta Main Road, Bangalore – 560 090.
2007-2008
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
KARNATAKA, BANGALORE
ANNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION
1 / Name of the candidate and address /Mr. PANKAJ N. PATEl
11, Panghat row house,Opp. Karunasagar temple,
Parlepoint,
Umara,
Surat-395007
Gujarat.
2 / Name of the Institution / Acharya & B.M. Reddy college of pharmacy#89/90, Soldevanahalli,
Chikkabanavara (post),
Hesaraghatta Main Road,
Bangalore-560 090.
3 / Course of the study and subject / M. Pharmacy
(Pharmaceutics)
4 / Date of admission / June-2007
5 / Title of topic
“FORMULATION DEVELOPMENT AND EVALUATION OF SERTRALINE HYDROCHLORIDE BUCCAL PATCHES.”
6
6.1 / BRIEF RESUME OF INTENDED WORK
Need for the study:
Oral mucosal drug delivery is an alternative method of systemic drug delivery that offers several advantages over both injectable and enteral methods. Because the oral mucosa is highly vascularised, drugs that are absorbed through the oral mucosa directly enter the systemic circulation, bypassing the first-pass metabolism in the liver.
The oral cavity is highly acceptable by patients. The Buccal mucosa is relatively permeable with a rich blood supply; it is robust and shows short recovery times after stress or damage.
Buccal mucosa also gives rapid absorption of drugs than oral route. Buccal film may be preferred over adhesive tablet in terms of flexibility and comfort.
Sertraline hydrochloride belongs in class of antidepressants and categorized in selective serotonin reuptake inhiditor (SSRI). The mechanism of action of Setraline is presumed to be linked to its inhibition of CNS neuronal uptake of serotonin (5HT). In vitro studies in animals also suggest that Sertaline is potent and selective inhibitor of neuronal serotonin reuptake and has only very weak effect of norepinephrine and dopamine neuronal reuptake. In vitro studies have shown that Sertraline has no significant affinity for agrenergic (alpha 1, alpha2, beta), cholinergic, GABA, dopaminergic, histaminergic, serotonergic (5HT1A, 5HT1B, 5HT2), or benzodiazepine receptors; antagonism of such receptors has been hypothesized to associated with various anticholinergic, sedative, and cardiovascular effects for other psychotropic drugs. Its oral bioavailability is only 44%.1
One of the most feasible drug delivery system for such a drug is in the form of buccal patches, which provides better management of the disease, improves drug bioavailability and patient compliance.
6.2 / REVIEW OF LITERATURE:
Mucoadhesive buccal films of Diltiazem hydrochloride using Sodium CMC, polyvinyl pyrrolidone K-30 and polyvinyl alcohol were formulated. The films were evaluated on the basis of their physical characteristics as well as the bioadhesive performance of various films 2.
Mucoadhesive buccal patches of Diclofenac Sodium are designed using polyvinyl alcohol, hydroxy ethyl cellulose and chitosan. Swelling and bioadhesive characteristics were determined for both plain and medicated patches. Patches were studied for physical characteristics 3.
Buccal films of Salbutamol Sulphate are formulated using different polymers in various proportions and combinations. The physicochemical parameters and drug release characteristics were evaluated in order to study effect of polymer and it’s concentration on the drug release 4.
Mucoadhesive Film are developed using polyvinyl pyrrolidone (PVP) as film forming polymer and carboxy methylcellulose Sodium salt (NaCMC) as mucoadhesive polymer and was loaded with Ibuprofen. They were performed In vitro and in vivo release studies and evaluated swelling, mucoadhesion and organoleptic characteristics 5.
The examination of penetration rate of lidocaine (LC) through excised oral mucosa from hamster cheek pouch and the in vitro release rate of LC from film dosage forms with hydroxypropylcellulose (HPC) as a film base. Addition of glycyrrhizic acid (GL) to the HPC films increased the LC release rate almost GL-content-dependently, while an optimum GL content was observed for the LC penetration rate. No LC penetration was observed from an acidic aqueous solution (pH 3.4) of LC, suggesting only unionized LC can substantially penetrate through the mucosa. A significant relationship between the penetration rate of LC and the release rate of unionized LC was found, suggesting that the in vitro dissolution study is a useful tool to predict the penetration rate taking the unionized drug fraction into consideration 6.
The formulation of gelatin films are developed with a view to producing sustained-release films of lignocaine for application to the buccal cavity is described. Both dissolution and diffusion controls were investigated as possible mechanisms for prolonging drug release. It was found that although the physical properties of the films were markedly affected by changing the formulations, the prolongation in release were insufficient for the proposed clinical applications. Increased cross-linking of the gelatin strands with formaldehyde produced more rigid films than controls but diffusion of lignocaine through them was unaltered 7.
The systemic absorption of Propranolol Hydrochloride was studied from Buccoadhesive films delivered through rabbit oral mucosa with unidirectional drug release system. Films were fabricated using Sodium carboxy methylcellulose, Carbopol (CP) 934 and polycarbophil 8.
The bioadhesive properties of several different Mucoadhesive buccal patches were assessed. The patches consisted of co formulations of Silicon polymers and Carbopol 934P. They have measured for each of the test formulations, using an ophthalmic shadow scope. They also calculated adhesion between the water and the patches (w1), and between the patches and freshly excised rabbit buccal mucosa (w2). The results of the contact-angle measurements indicated that the contact angle decreased with an Increase in the amount of Carbopol in the formulation 9.
Mucoadhesive buccal patches are prepared and evaluated in vitro and in vivo using rats for release of Thyrotropine-releasing hormone (TRH). TRH (10%w/w) was incorporated in patches co formulated with silicon And organic polymers and its release profile was characterized 10.
Mucoadhesive films of Miconazole Nitrate were designed and evaluated using different polymers like HPMC-E4 M, HPC-M and Carbopol 934- P. The film was evaluated on the basis of their physical characteristics 11.
Mucoadhesive buccal films of Clotrimazole were designed using different polymers and propylene glycol. The films were evaluated for their physical characteristic12.
6.3 / OBJECTIVE OF THE STUDY:
Following are the objectives of the present study: -
1. To carry out preformulation studies for possible drug-polymer interactions by IR/DSC.
2. To design and develop buccal patches of Sertraline Hydrochloride.
3. To formulate the drug delivery system using various excipients.
4. To evaluate the buccal patches using following parameters:
i. Surface pH.
ii. Swelling studies.
iii. Weight uniformity.
iv. Patch thickness.
v. Folding endurance of the patch.
vi. In vitro Bioadhesive studies.
vii. In vitro Release studies.
viii. Ex vivo Permeation studies for 24 hours.
5. To carry out short term stability studies on the most satisfactory formulation as per ICH guidelines at 30 ± 20C (65 ± 5 %RH) and 40 ± 20C (75 ± 5 %RH).
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7.1
/MATERIALS & METHODS
SOURCE OF DATA:
1. Review of literature from:a. Journal such as
I. Indian Journal of Pharmaceutical Sciences
II. European Journal of Pharmaceutical Sciences
III. Journal of Controlled Release
IV. International Journal of Pharmaceutical Sciences
V. Drug Development and Industrial Pharmacy
VI. Indian Drugs
b. World Wide Web.
c. I.I.Sc Library, Bangalore.
d. J-Gate@Helinet
e. R.G.U.H.S. Library, Bangalore.
7.2 / METHODS OF COLLECTION OF DATA:
1. Preformulation studies for possible drug-polymer interactions by IR/DSC analysis.
2. Preparation of buccal patches using different excipients.
3. To evaluate the formulated mucoadhesive buccal patches using following parameters:
a. Surface pH.
b. Swelling studies.
c. Weight uniformity.
d. Patch thickness.
e. Folding endurance of the Patch.
f. In vitro Muco/Bioadhesive studies using Porcine Buccal Membrane.
g. In vitro release studies using U.S.P. Dissolution Test Apparatus (Paddle over Disk Type) in Phosphate buffer pH 6.8.
h. Ex vivo release studies through porcine buccal mucosa into Phosphate buffer for 24 h using diffusion cell.
4. To carry out short term stability studies on the most satisfactory formulation as per ICH guidelines at 30 ± 20C (65 ± 5 %RH) and 40 ± 20C (75 ± 5 %RH).
7.3 / Does the study require any investigation or investigation to be conducted on patient or other humans or animals?
“NO”
7.4 / Has ethical clearance been obtained from your institution in case of 7.3?
“NOT APPLICABLE”
8 / LIST OF REFERENCES1. http://www.drugs.com/pro/sertraline.html and http://en.wikipedia.org/wiki/Sertraline, operated on date 21st Nov. 2007
2. Semalty A, Bhojwani M, Bhatt K, Gupta GD, Shrivastav AK. Design and Evaluation of Mucoadhesive Buccal Films of Diltiazem Hydrochloride. Ind. J. Pharm. Sci. 2005; 67 (5): 548-552.
3. Panigrahi L, Pattnaik S, Ghosal SK. Design and Characterization of Mucoadhesive Buccal Patches of Diclofenac Sodium. Ind. J. Pharm. Sci. 2005; 67 (3): 319-326.
4. Pavankumar GV, Ramakrishna V, William GJ, Konde A. Formulation and Evaluation of Buccal Films of Salbutamol Sulphate. Ind. J. Pharm. Sci. 2005; 67 (2): 160-164.
5. Luana P, Ambroji V, Angelici F, Ricci M, Giovagnoli S, Capuceella M and Rossi C. Development of Mucoadhesive Patches for buccal administration of Ibuprofen. J. of Cont. Rel 2004; 99 (1): 73-82.
6. Hirokazu Okamoto, Hirohisa Taguchi, Kotaro Iida and Kazumi Danjo. Development of Polymer Film Dosage Forms of Lidocaine for Buccal Administration: I. Penetration Rate and Release Rate. J. of Cont. Rel. 2001; 77 (3): 253-260.
7. A. Li Wan Po and J. R. Mhando. Formulation of Sustained-Release Products: Dissolution and Diffusion-Controlled Release from Gelatin Films. Int. J. of Pharmaceutics 1984; 20 (1-2): 87-98.
8. Balmurugan K, Pandit JK, Choudary PK, Balasubramaniam J. Systemic Absorption of Propranolol Hydrochloride from Buccoadhesive Films. Ind. J. Pharm. Sci. 2001; 63(6): 473-480.
9. Li. C, Bhatt PP, and Johnston TP. Evaluation of a Mucoadhesive Buccal Patch for Delivery of Peptides: In vitro Screening of Bioadhesion. Drug. Dev. Ind. Pharm. 1998; 24 (10): 919-926.
10. Li C, Koch L, Raul VA, Bhatt PP. Absorption of Thyrotropine-releasing Hormone in Rats using a Mucoadhesive buccal patch. Drug. Dev. Ind. Pharm. 1997; 23 (3): 239-246.
11. Khurana R, Ahuja A, Khar R. Development and Evaluation of Mucoadhesive Films of Miconazole Nitrate. Ind. J. Pharm. Sci. 2000; 6: 447-453.
12. Khanna R, Agarwal S. Preparation and Evaluation of Mucoadhesive Buccal Films of Clotrimazole for oral Candida infection. Ind. J. Pharm. Sci. 1997; 59 (6): 299-305.
9 / Signature of the candidate:
10 / Remarks of the Guide: / Recommended
11 / Name and Designation of:
11.1 Institutional Guide: / Mrs. S. Anitha
Asst. Professor
11.2 Signature:
11.3 Co-Guide:
11.4 Signature: /
11.5 Head of the Department: / Dr. Roopa Karki
Dept. of Pharmaceutics
11.6 Signature
12 / 12.1 Remarks of the Principal / Recommended
12.2 Signature
/
Dr. Goli Divakar
Principal
Acharya & B.M.Reddy College of Pharmacy,#89/90, Soldevanahalli,
Chikkabanavara (post),
Hesaraghatta Main Road,
Bangalore-560 090.