FORMULATION AND DEVELOPMENT OF IMMEDIATE RELEASE TABLETOF SOLIFENACIN SUCCINATE USING DIFFERENT POLYMER
M.Pharm. Dissertation Protocol
SUBMITTED TO THE
RajivGandhiUniversity of Health Sciences, Karnataka
Bangalore.
BY
HITENDRA ARJUNSINGH CHAUHAN
DEPARTMENT OF PHARMACEUTICS
DISSERTATION PROTOCOL
SUBMITTED TO THE
RAJIVGANDHIUNIVERSITY OF HEALTH SCIENCES
BANGALORE- 560041,
KARNATAKA.
UNDER THE GUIDANCE OF
Prof. Dinesh B.S
H.O.D
DEPARTMENT OF PHARMACEUTICS
2012-2013
PRIYADARSHINICOLLEGE OF PHARMACY
KORTAGERE,TUMKUR
KARNATAKA
RAJIVGANDHIUNIVERSITY OF HEALTH SCIENCES,
KARNATAKA, BANGALORE
ANNEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1. / NAME OF THE CANDIDATEANDADDRESS (IN BLOCK LETTERS) / HITENDRA ARJUNDSINH CHAUHAN
HOUSE NO.5,JAY JADESWAR SOCIETY,NEAR SONERIA BLOCKS,BAPUNAGAR,AHAMDABAD,GUJARAT,380024
2. / NAME OF THE INSTITUTION / PRIYADARSHINICOLLEGE OF PHARMACY
KORTAGERE,TUMKUR, 572129
KARNATAKA
3. /
COURSE OF STUDY AND SUBJECT
/ M. PHARMPHARMACEUTICS.
4. / DATE OF ADMISSION OF COURSE / July’2012
5. /
TITLE OF TOPIC
/ FORMULATION AND DEVELOPMENT OF IMMEDIATE RELEASE TABLET OF SOLIFENACIN SUCCINATE USING DIFFERENT POLYMER6. / BRIEF RESUME OF THE
INTENDED WORK
6.1 Need for the study
6.2 Review of the literature
6.3 Objectives of the study / ENCLOSURE-I
ENCLOSURE-II
ENCLOSURE-III
7. /
MATERIALS AND METHODS
7.1 Source of data7.2 Method of collection of data
7.3 Does study require any Investigations or interventions to be conducted on patients or Other human or animal? If so, Please describe briefly.
7.4 Has ethical clearance been obtained from your institution in case of 7.3 / ENCLOSURE-IV
ENCLOSURE-V
ENCLOSURE-VI
ENCLOSURE-VII
8. / LIST OF REFERENCES / ENCLOSURE-VIII
9. / SIGNATURE OF CANDIDATE
10. / REMARKS OF GUIDE / Recommended for approval
11. / NAME AND DESIGNATION OF
11.1 Guide
11.2 Signature
11.3 Co guide (if any)
11.4 Signature
11.5 Head of department
11.6 Signature / Prof. Dinesh B.S.
H.O.D
DEPARTMENT OF PHARMACEUTICS,
PRIYADARSHINICOLLEGE OF PHARMACY,
KORTAGERE,TUMKUR, 572129
KARNATAKA.
Not applicable
Not applicabl
Prof. Dinesh B.S.
H.O.D
DEPARTMENT OF PHARMACEUTICS,
PRIYADARSHINICOLLEGE OF PHARMACY,
KORTAGERE,TUMKUR, 572129
KARNATAKA
12. / 12.1 Remarks of the
Chairman and principal
12.2 Signature / SUBMITTED FOR APPROVAL
6. / BRIEF RESUME OF THE INTENDED WORK
ENCLOSURE-I
6.1 Need for the study
Oral drug delivery is the most desirable and preferred method of administering therapeutic agents for their systemic effects. Many drug substances, conventional, immediate release formulations provide clinically effective therapy while maintaining the required balance of pharmacokinetic and pharmacodynamic profiles with an acceptable level of safety to the patient.1
Immediate Release Tablets are those tablets which are designed to disintegrate and release their medication with no special rate controlling features, such as special coatings and other techniques2. Immediate release (IR) tablets are a better choice for drugs which need to elicit their action in a short duration. IR tablets are intended to disintegrate in the stomach, where the pH is acidic. Immediate release tablet should disperse; disintegrate in less than three minutes and must release 85% or more of stated amount of drug within 30 min.3 Recently immediate release tablets have started gaining popularity and acceptance as a drug delivery system, mainly because they are easy to administer, has quick onset of action, it is economical and lead to better patient compliance. They are also a tool for expanding markets, extending product life cycles and generating opportunities 4,5,6.
Solifenacin is a urinaryantispasmodic of the antimuscarinic class. It is used in the treatment of overactive bladder with or without urge incontinence. Solifenacin is a competitivemuscarinic acetylcholine receptorantagonist.
The current investigation is concerned with design and characterization of oral immediate release tablets of Solifenacinto dissolve in the gastrointestinal contents, with no intention of delaying or prolonging the dissolution or absorption, thereby improving the efficacy and better patient compliance.
ENCLOSURE II6.2Review of literature
- Bokshi et al.,7Formulated, developed, optimized and in-vitro evaluated of immediate release allylestrenol tablets. To minimize critical process parameters and since allylestrenol is heat sensitive, direct compression method was selected for the formulation of immediate release allylestrenol tablets. Tablets were prepared using cross carmellose sodium, crosspovidone, pre gelatinized starch and sodium starch glycolate as disintegrants. During the course of study it was found that the formula G4 containing sodium starch glycolate as disintegrant exhibited acceptable disintegration time, percentage drug content per tablet and in vitro drug release. So at last it was concluded that immediate release allylestrenol tablets can be prepared using direct compression which met the required specifications.
- Yeole et al.,8PreparedParoxetine immediate release tablet by direct compression method. Effect of various fillers and disintegrants were also explored. Microcrystalline cellulose, Galen IQ and dicalcium phosphate were used as directly compressible fillers. In order to obtain acceptable product several trials were conducted. Various pharmacopoeial evaluations of the formulations were conducted including weight variation, hardness, disintegration time, friability and in-vitro dissolution. Final selection of formulation was done based on pharmaceutical equivalence of development formulation to that of marketed one.
- Hu et al.,9 Prepared the immediate release tablet by using dry granules. The preparation was optimized by using orthogonal design which took the flow property of granules, the hardness, the disintegrating time and the dissolution rate of the tablet as indices. The optimized formulation contained 40% microcrystalline cellulose, 10% sodium carboxymethyl starch and 15% dextrin. The hardness disintegrating time and T50 of the tablet were 4.5 kg, 3 min, 5 min respectively. The preparation on immediate release tablet using the optimized formula above was successful.
- Shiyani B et al .,10 The present study involve the Formulation and Evaluation of Bi-layer Tablet of Metoclopramide Hydrochloride and Ibuprofen. In this formulation Metoclopramide Hydrochloride was formulated as an immediate release layer by using various disintegrants like Ac-Di-Sol, Polyplasdone XL, Explotab, Agar and Gellan Gum. Ibuprofen was formulated as sustained release layer using hydrophilic matrix [hydroxyl propyl methyl cellulose] (HPMC K4M).
- Mandal U et al.,11 The current study involve the Formulation and In Vitro Studies of a Fixed-Dose Combination of a Bilayer Matrix Tablet Containing Metformin HCl as Sustained Release and Glipizide as immediate Release, using hydroxy propyl methyl cellulose (HPMC) as the matrix-formingPolymer was reported. Three different grades of HPMC (HPMC K 4M, HPMC K 15M, and HPMC K 100M) were used.
- Atram SC, et al.,12 The present study involve the Formulation of bilayer tablets containing Metoprolol Succinate as sustained release layer using polymers such as HPMC K4M and Starch 1500 and Amlodipine besylate as immediate release layer using super- disintegrants such as sodium starch glycolate and Microcrystalline Cellulose, by wet granulation method was reported.
- Kulkarni A, Bhatia M.13 The present study involve the Bilayer floating tablets of Atenolol as sustained release layer and Lovastatin as immediate release layer were prepared by direct compression using sodium starch glycolate as a superdisintegrant and HPMC K100M and Xanthan gum as the release controlling polymer and sodium bi-carbonate as a gas generating agent was reported.
- Kannan K et al.,14 Have said that Emtricitabineand disoproxil fumarate belongs to class of anti-retroviral drugs known as nucleotide analogue reverse transcriptase inhibitors. They formulated and evaluated an immediate release tablet of emtricitabine and tenofovir disoproxil fumarate using different disintegrants. Preformulation studies were performed prior to compression. The tablets were compressed using microcrystalline cellulose, lactose, pregelatinized starch, croscarmellose sodium, talc, sodium starch glycolate, magnesium stearate and opadry 11 blue was used for coating the tablets.
- Kaushic,15 Immediate Release tablets of promethazine theoclate were prepared by direct compression method after incorporating super disintegrants ac-di-sol and sodium starch glycolate and Crosspovidone in different concentrations. Nine formulations having super disintegrants at different concentration levels were prepared to assess their efficiency and critical concentration level. Different types of evaluation parameter for tablet were used. Tablets containing ac-di-sol salt showed superior organoleptic properties along with excellent in-vivo and in-vitro dispersion time and drug release, as compare to other formulations.
- Lalla J K and Mamania H M.16 Immediate release tablets of salbutamol sulphate were prepared using sublimable ingredients. Selection of the fillers also had an important role in deciding the disintegration time. Evaluation of the tablets showed that all the tablets were found to be within official limits and the disintegration time for the formulation range from 5s to 40s.
6.3 Objectives of the study
1. To select suitable polymers and super disintegrantsfor the preparation of IR tablest.
2. To formulatedevelopSolifenacinimmediate release tablets.
3. To evaluate the pre-compression parameters.
4. To evaluate the post-compression parameters.
5. To carry out in-vitrorelease study of tablets.
MATERIALS AND METHODS:
Materials:
Drug: Solifenacin Succinate.
Super disintegrant: Ac-Di-Sol, Crospovidone, Sodium Starch Glycolate, Kollidone,
L-Hydroxy propyl methyl cellulose,croscarmellose sodiumetc.
Polymers: Different grades of Hydroxy Propyl Methyl Cellulose (like HPMC K4M,
HPMC K100M, HPMC E50 LV etc.) Eudragit S, Eudragit LR 100 and
Sodium Carboxy Methyl Cellulose, Hydroxy Propyle Cellulose.etc.
Methods:
SolifenacinSuccinate immediate release tablets will be prepared byDirect compression.
method, Wet granulation etc.
ENCLOSURE-IV
7.1. Source of Data
1) Review of literature from :
a. Journals : such as
- Indian journal of pharmaceutical sciences.
- International journal of comprehensive pharmacy.
- International journal of pharmaceutical research.
- European journal of pharmaceutical sciences.
- International journal of pharmaceutical sciences and Nanotechnology.
- AAPS Pharmaceutical Science & Technology.
- International journal of pharmaceutical & Technical Research.
- England Journal of Medicine.
- Journal of Controlled Release
- AAPS Pharm.Sci.Tech.
- Acta Poloniae Pharmaceutica and Drug Research
- Asian Journal of Pharmaceutical Sciences
- Advanced Drug Delivery Reviews.
- Journal of Pharmacy Research.
- International Journal of Chem. Tech Research.
b. Internet browsing.
- J-Gate@Helinet.
- RGUHS e-Library
-
2) Library: xxxxxx College of Pharmacy.
3) Laboratory based studies.
ENCLOSURE-V
7.2. Method of Collection of Data
Data on drugs will be collected through literature survey and from physiochemical
database. Extensive preformulation trials would provide the basis for selection of
the suitable excipients and system for final formulation development.
1. Preformulation studies
a) Drug-polymer compatibility studies
b) pre-compression parameters evaluation :
- Bulk densityTapped densityTrue density.
- Porosity.
- Angle of repose.
- Haunser ratioCarr’s index.
- Moisture content.
- Direct compressionor wet granulation method.
- Post-compression parameters evaluation:
- Shape & size.
- Weight variation test.
- Thickness.
- Hardness& Friability.
- Drug content uniformity.
- in-vitro disintegration & dissolution time.
7.3. Does the study require any investigation or intervention to be conducted on patients or other humans or animals? If so, please mention briefly.
-NO-
ENCLOSURE-VII
7.4. Has ethical clearance been obtained from your institution in case of 7.3?
-NOT APPLICABLE-
ENCLOSURE-VIII
LIST OF REFERENCES
- Ramanathan et al., Pharmacokinetics of emtricitbine, tenofovir, and GS-9137 following co administration of emtricitabine, tenofovir disoproxil fumarate and ritonavir-boosted GS-9137. J AIDS 2007;45(3):274-79.
- Shishu, BhattiA. Fast disintegrating tablets of Diazepam.Indian Drugs 2006; 43:643-8.