A STUDY OF FORMULATION AND PROCESSING FACTORS INFLUENCING THE RELEASE OF CARVEDILOL
M. Pharm. Dissertation Protocol
Submitted to the
Rajiv Gandhi University of Health Sciences, Karnataka
Bangalore.
By
BOHNSLE SHALINI
B.Pharm.
Under the Guidance of
Dr. N.G.RAGHAVENDRA RAO
Professor
DEPARTMENT OF PHARMACEUTICS
N.E.T. PHARMACY COLLEGE
RAICHUR
2008.
Rajiv Gandhi University of Health Sciences, Karnataka
Bangalore
ANNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1 / Name of candidate and address (In Block Letters) / BOHNSLE SHALINIH.NO 11/10/132/1/A, PLOT NO 2, INDIRANAGAR COLONY, ADJ TO TELEPHONE COLONY,
HYDERABAD-500 035.
ANDHRA PRADESH.
2 / Name of the Institute / N.E.T.PHARMACY COLLEGE, RAICHUR.
3 / Course of study and subject: / M.PHARM. PHARMACEUTICS.
4 / Date of admission of course: / 10-06-08.
5 / Title of the topic:
“A STUDY OF FORMULATION AND PROCESSING FACTORS INFLUENCING THE RELEASE OF CARVEDILOL”.
6 / Brief Resume of this intended work:
6.1 Need for the study Enclosure-I
6.2 Review of Literature Enclosure-II
6.3 Objectives of study Enclosure-III
7 / Materials and Methods:
7.1 Source of data Enclosure-IV
7.2 Method of collection of data (Including sampling procedure, if any)
Enclosure-V
7.3 Does the study require any investigation or interventions to be conducted on patients of humans or animals? If so, please describe briefly.
------NO------
7.4 Has ethical clearance been obtained from your institution in case of 7.3?
------NOT APPLICABLE------
8 / List of References Enclosure-VI
9 / Signature of the candidate
10 / Remarks of the Guide / The proposed work can be carried out in the laboratory. Protocol is as per university guidelines.
11 / Name and designation of (in block letters)
11.1 Guide
11.2 Signature / Dr. N.G.RAGHAVENDRA RAO
Professor
Dept. of Pharmaceutics
N.E.T. Pharmacy College,
Raichur-584 103.
11.3 Co-Guide (if any)
11.4 Signature / ------
------
11.5 Head of Department
11.6 Signature /
Dr. H. DODDAYYA
Professor
Dept. of pharmaceutics
N.E.T. Pharmacy college,
RAICHUR- 584 103.
12 / 12.1 Remarks of the Chairman and Principal
12.2 Signature / Dr. H. DODDAYYA
Principal
N. E. T. Pharmacy College,
RAICHUR-584 103.
Enclosure-I
6)Brief resume of the intended work:
6.1)Need for the study:
The oral route of administration still continues to be the most preferred route due to it’s manifold advantages including ease of ingestion, pain avoidance, versatility and most importantly patient compliance.1 Oral solid dosage forms are popular because of ease of administration, accurate dosage, self medication, pain avoidance and most importantly patient compliance.2 Among the pharmaceutical dosage forms, the conventional tablet seems to be most popular, because of its ease of transportability and comparatively lower manufacturing cost.3
There are several factors other than physicochemical properties of the drug that may influence the dissolution rate and hence, bioavailability of drugs from the solid dosage forms. It has been shown that, the dissolution rate of pure drugs can be altered significantly by the proper selection of formulation components as well as processing methods.4 Reports related to effect of formulation excipient like diluents 5, disintegrants6, surfactants7, granulating agents8 and binders9 are available. In other set of works, effect of processing factors such as method of granulation10 on the dissolution rate have been reported. Ho and Hersey11, have introduced a novel method of granulation based on the agglomeration due to prolonged grinding to improve the dissolution rate of paracetamol from tablets.
Carvedilol is both an alpha and a beta adrenoreceptor-blocking agent, that is chemically described as 1-(9H-carbazol-4-yloxy)-3-[2-(2-methoxyphenoxy) ethylamino] propan-2-ol, used in treatment of various cardiovascular disorders such as angina pectoris, cardiac arrhythmia and hypertension with oral bioavailability of 25-35%and its half-life is about 7-10 hours12. Therefore, the main objective of the present investigation is to study the various formulations and processing variables to modify the dissolution rate of the carvedilol from formulations.
Enclosure-II
6.2)Review of literature:
1)Finhold P and Solvang S6 prepared phenobarbital tablets by both wet and dry granulation keeping all the formulation factors constant, both procedures gave rates of release provided that disintegrant (starch) was incorporated and mixed with the drug before dry granulation.
2)Marlowe E and Shagraw R8 studied the dissolution of sodium salicylate tablets prepared by both wet granulation and direct compression methods. They found that tablets prepared by direct compression with spray-dried lactose uniformly exhibited more rapid and complete dissolution profiles compared to those prepared by wet granulation.
3)Chebli C and Cartilier L9 evaluated properties of new tablet binding/ disintegrating agent, cross-linked cellulose (CLC) in comparision with binding/disintegrating agents widely used in tablet manufacture such as Aricel PH 101 and Arisil PH 102. The effect of CLC-C25 concentration on the physical properties of direct compressed tablets was also studied. CLC-C25 demonstrated good binding/ disintegrating properties.
4)Karavas E, Georgarakis E and Bikiaris D13 have prepared pulsatile release formulations consisting of two layered tablets appropriate for preventing ischemic heart disease. For this reasons the active core was constituted by a felodipine/PVP 10/90 w/w solid dispersions. Upon exposure of the prepared tablets to the release medium it was found that the drug release rate is directly attributed to the size of these nanodispersions while PVP/felodipine 90/10 w/w corresponds to an immediate release at an interval less than 30 minutes.
5)Abrahamson B, Johansson D, Torstensson A and Wingstrand K14 have reported the release of felodipine, a water insoluble drug by using sodium laurly sulphate (SLS), polyoxyethylene 20 sorbitan mono oleate (TWEEN) or cetyl trimethyl ammonium bromide (CTAB) in the test medium as solubilizers. The study revealed that addition of solubilizers is a feasible way to obtain sink condition for the in vitro release testing of ER formulations containing water insoluble drugs. However, the choice of solubilizer must be carefully evaluated due to the possibility of interactions between the solubilizer and release rate controlling excipients in the dosage form.
6)Vasilios I, Teberekidis, Michael P and Sigalas15 have studied the effect of hydrogen bonding in solid dispersions of antihypertensive and antianginal drug of felodipine with the polyvinylpyrrolidone (PVP) or polyethylene glycol (PEG) water-soluble polymers. Interaction energies, electron density, laplacian and vibrational data showed a stronger hydrogen bond of felodipine with PVP polymer in comparison to that with PEG.
7)Sreenivas SA, Dandagi PM, Gadad AP, Godbole AM, Hiremath SP and Mastiholimath VS16 prepared ondansetron hydrochloride mouth disintegrating tablets using various disintegrants like crospovidone, croscarmellose sodium, pregelatinized starch, sodium starch glycolate and L-HPC in 5% and 10% concentrations and by direct compression, and reported that tablets containing 10% disintegrant concentration of crospovidone and croscarmellose sodium were best for ondansetron hydrochloride mouth disintegrating tablets.
8)Gohel M, Patel M, Avani A17 prepared mouth dissolving tablets of nimesulide by preparing granules containing nimesulide, camphor, crospovidone and lactose and then camphor was sublimed from granules, alternatively, first tablets were prepared and then camphor was sublimed by vacuum. Sublimation of camphor from tablets resulted in superior tablets as compared with tablets prepared from granules that were exposed to vacuum.
9)Lalla JK and Mamania HM18 prepared inclusion complex of rofecoxib, NSAID with beta-cyclodextrin using ball milling technique and evaluated using DSC. Fast dissolving tablet composition with 25 mg equivalent rofecoxib showed complete release of rofecoxib in 12 minutes as compared to 20% drug release from the conventional release marketed tablets during the same period.
10)Kumar KN, Babu GVMM, Prasad CH, Himasankar K, Seshasayana A and Murthy RV19 have prepared solid mixtures (by physical mixing, co-grinding and kneeding method) of poorly water soluble drug meloxicam with an intention to enhance the dissolution of the drug. It was found that co-grinding method comparatively more effective.
11) Sharma S, Gupta GD, Jain CP and Naruka PS20 prepared carvedilol fast dissolving tablet by using drug solid dispersion in polyethylene glycol. The tablets were prepared using Ac Di Sol and crossprovidone as disintegrating agents by direct compression technique. It was found that the tablets prepared by Ac Di Sol showed faster disintegration than crossprovidone.
Enclosure-III
6.3) Objective of the study:
The present study is planned with the following objectives:
1)To develop newer formulation for carvedilol.
2)To evaluate the formulations with respect to various physical parameters (weight variation, hardness and friability.)
3)To evaluate the tablets with respect to content uniformity, in vitro release studies, etc.
4)To characterize the formulation with respect to drug-excipient interaction (using
DSC and FTIR).
5) To carry out stability studies as per ICH guidelines.
Enclosure-IV
7) Materials and Methods:
7.1) Source of data:
Primary data: This data will be collected by conducting laboratory experiments and
recording the observation.
Secondary data: This will be collected from various journals and textbooks.
Enclosure-V
7.2) Method of collection of data:
The data for the study is planned to collect from the laboratory based experiments, which include the following –
Preparation of newer formulations of Carvedilol.
Evaluation of newer formulation with respect to drug content determination,
In vitro release studies.
Evaluation of newer formulation with respect to some physical parameters (weight variation, hardness and friability.)
Enclosure- VI
8) List of references:
1)Kuchekar BS ,Bhise SB,Arumugam V. Design of fast dissolving tables.Ind J Pharm Edu 2001;35(4): 150-2.
2)Chien YW. Novel drug delivery systems.2nd Ed. New York: Marcel Dekker; 1992.
3)Reddy LH, Ghosh B, Rajneesh. Fast dissolving drug delivery systems: A review of the literature. Ind J Pharm Sci 2002; 64(4): 331-6.
4)Abdou HM. (Ed). Factors affecting the rate of dissolution of solid dosage forms. In; Dissolution, bioavailability and bioequvalence.pp 73-105. Mack publishing company eastonpennsvivanio.
5)Albertini B, Cavallari C, Passerini N. Evaluation of beta- lactose, PVP K12 and PVP K90 as excipients to prepare piroxicam granules using two wet granulation techniques. Eur J Pharm Biopharm 2003; (56): 479-87.
6)Solvang S, Finhold P. Phenobarbital tablets by wet and dry granulation methods. J Pharm Acta Helv 1970; ibid 59: 49.
7)Chen LR, Wesley JA, Bhattachar S, Ruiz B, Bahash K, Babu SR. Dissolution behaviour of a poorly water soluble compound in the presence of Tween 80.Pharm Res.2003; 20(5): 797-801.
8)Marlowe E, Shagraw R. Sodium salicylate tablet using wet granulation and direct compression methods.J Pharm Sci1967; 56: 498.
9)Chebli C, Cartilier L. Cross linked cellulose as a tablet excipient: A binding/disintegrating agent. Ind J Pharm 1998; 171: 101-10.
10)Sanderson IM, Kennerley JW, Parr GD. An overview of the relative importance of formulation and process variables using factorial design. Pharmcol 1984; 36(12): 789-95.
11)Ho T, Hersay J. Compatability of granules prepared by a novel method of granulation and their dissolution. J Pharm Pharmcol 1980; 32(3): 160-6.
12) Carvedilol drug profile.
13)Karavas E, Georgarakis E, Bikiaris D. Felodipine nanodispersion as acive core for predictable pulsatile chromotherapeutics using PVP/HPMC blends as coating layer. Int J Pharm 2006; 313: 189-197.
14)Abrahamson B, Johnsson D, Torstensoon A, Wingstrand K. Evaluation of solubilizers in the drug release testing of hydrophilic matrix extended release tablets of felodopine. Pharm Res Vol II. 1994; 1093-97.
15)Vasilios I, Teberkidis, Michael P, Sigalas. Theoretical study of hydrogen bond interaction of felodipine with PVP and PEG J Mol Str. 2006; 1-3.
16)Sreenivas SA, Dandagi PM, Gadad AP, Godbole AM, Hiremath SP, Mastiholimath VS. Formulation and evaluation of ondensetron hydrochloride directly compressed mouth-disintegrating tablets. Ind Drugs 2006; 43(1): 35-8.
17)Gohel.M, Patel M, Amin A, Agarwal R, Dave R, Bariya N. Formulation design and optimization of mouth dissolve tablets of nimesulide using vacuum drying technique AAPS Pharm.SciTech 2004; 5(3): 1-6.
18) Lalla JK, Mamania HM. Fast dissolving refecoxib tablets. Ind J Pharm Sci 2004; 350-2.
19)Kumar KN, Babu GVMM, Prasad CH, Himashankar K, Seshasayana A, Murthy RV. Comperative studies on effect of some hydrophilic polymers on dissolution rate of poorly soluble drug, Meloxicam. Ind Drugs 2002; 39(6): 323.
20)Sharma S, Gupta GD, Jain CP and Naruka PS. Fast dissolving tablet: A novel approach for delivery of carvedilol.
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