“Formulation and Evaluation of Osmotically Controlled Oral Drug Delivery System containing acarbose”

MASTER OF PHARMACY DISSERTATION PROTOCOL

SUBMITTED TO THE


RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES KARNATAKA,

BANGALORE.

BY

ROSHAN M A

M.Pharm

Under The Guidance of

Mr.SRIPATHY D.M.Pharm

Asst.Professor

DEPARTMENT OF PHARMACEUTICS.

SRINIVAS COLLEGE OF PHARMACY, VALACHIL, MANGALORE – 574143

2013-2015

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

BANGALORE, KARNATAKA

ANNEXURE-II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. / Name of the Candidate and Address: / Mr.ROSHAN M A
1stYEARM.PHARM,
DEPT. OF PHARMACEUTICS,
SRINIVAS COLLEGE OF PHARMACY,
VALACHIL, MANGALORE-574143.
2. / Name of the Institution: / SRINIVAS COLLEGE OF PHARMACY,
VALACHIL,FARANGIPETE POST, MANGALORE-574143.
3. / Course of Study and Subject: / MASTER OF PHARMACY
(PHARMACEUTICS)
4. / Date of Admission: / 25/07/2013
5. / Title of the Project:
“FORMULATION AND EVALUATION OF OSMOTICALLY CONTROLLED ORAL DRUG DELIVERY SYSTEM CONTAINING ACARBOSE”
6. /

BRIEF RESUME OF THE INTENDED WORK:

6.1-NEED FOR THE STUDY:
Amongst the various route of drug delivery system, oral route is the most convenient and effective route preferred by patient. Treatment with rapid release conventional tablets requires multiple daily administrations, in order to maintain plasma concentration of drug within therapeutic window.Also such delivery systems have little control over the drug release and almost no control over the effective concentration at the target site. This kind of dosing pattern may result in unpredictable plasma concentrations.1,2
Oral controlled drug delivery dosage forms provide desired drug release pattern for longer period of time and so the rate and extent of drug absorption from oral controlled drug delivery formulations can be predicated. However, drug release from oral controlled release dosage forms may be affected by pH, GI motility and presence of food in the GI tract. But drug release from osmotic drug delivery system is not affected by physiological factors. The orally administered drugs in the form of conventional matrix or reservoir type formulation pose problems of bioavailability fluctuations due to gastric pH variation and hydrodynamic condition of the body.2,3
It is advantageous to deliver drugs which are to be given frequently for chronic ailments in the form of oral controlled release formulation. Osmotically controlled drug delivery system utilizes the principle of osmotic pressure for the controlled delivery of active agents. Drug delivery from this type of system is not influenced by different physiological factors within the gut lumen like pH. Also the release characteristic can be predicted easily from known properties of drug and dosage form. Thus they exhibit significant In-vitro In-vivo correlation.3
Diabetes mellitus is ametabolic disorder characterized by hyperglycaemia, glycosurea, hyperlipaemia, negative nitrogen balance andketonaemia. A widespread pathological change is thickening of capillary basement membrane, increase in vessel wall matrix and cellular proliferation resulting in vascular complications like lumen narrowing, early atherosclerosis, sclerosisof glomelular capillaries, retinopathy, neuropathy and peripheral vascular insufficiency. Two major types of diabetes mellitus are: Type І and Type ІІ.4
Acarbose is an oral alpha-glucosidase inhibitor for use in the management of diabetes mellitus. It is an oligosaccharide obtained from fermentation process of a microorganism, Actinoplanesutahensis. Acarbose is a white to off-white powder with a molecular weight of 645.6. It is soluble in water and has a pKa of 5.1. the plasma half-life of acarbose activity is approximately 2 hours in healthy volunteers.5
In the present work an attempt made to design and evaluate osmotically controlled oral drug delivery system containing acarbose for the treatment of Type ІІ diabetes mellitus.
6.2- REVIEW OF LITERATURE
Extensive review of literature published in various national and international journals, published articles in various official standard books, electronic media and websites is carried out.
  • Sandhya P, Hafsa S, Ayesha S, Sunitha M, Sunil R designedand evaluated Controlled release formulations of Glimepiride based on osmotic technology. Formulation F9 containing glimepiride, mannitol, PVP, MCC, aerosil, magnesium state and coating with CAP, dibutyl phthalate, PEG-400 was selected as optimized formulation. The effect of different formulation variable was studied to optimize release profile. The release rate increased significantly as the increase of osmogenratio from 1:0.5 to 1:1. The release rate increased significantly with the increase of concentration of pore forming agent (PEG-400) as noticed from the dissolution profile of the formulations. Thus drug release was inversely proportional to the concentration of osmogen in the core and the amount of pore forming agents in the coated tablets.6
  • Sameer S, Chandevar AV formulated and characterized an oral osmotic system which can deliver Lornoxicam for an extended period of time in a view to reduce the problems associated with the side effect of Non steroidal anti inflammatory drugs. Osmotic core tablet was prepared and coated with cellulose acetate. Pore was drilled with the help of mechanical microdrill and efforts are taken to improve release of NSAIDs in controlled passion without effect of food and other gastrointestinal factors. Different batches of Lornoxicamwas developed and evaluated In-vitro, in which batch 6b release (65.29%) the drug in controlled passion.7
  • Kanagale P, Braj LB, Mishra A, Davadra P, Kini R developed and evaluated Porous osmotic pump tablets, by mixing Oxybutynin with mannitol, lactose, povidone K30, isopropyl alcohol and coating with cellulose acetate, sorbitol and PEG400. The effectiveness of each formulation was measured as well as the release of the drug from osmotic pump tablets. It was concluded that drug release is increased with the amount of osmogent because of increased water uptake.8
  • Makhija SN, Vavia PR studied a controlled porosity osmotic pump-based drug delivery system, pseudoephedrine was chosen as a model drug with an aim to develop a controlled release system for a period of 12 h. Sodium bicarbonate was used as the osmogent. The effect of different ratios of drug:osmogent on the In-vitro release wasstudied. Cellulose acetate (CA) was used as the semipermeable membrane. Different channeling agents tried werediethylphthalate (DEP), dibutylphthalate (DBP), dibutylsebacate (DBS) and polyethyleneglycol 400 (PEG 400). It was found that drug release rate increased with the amount of osmogent due to the increased water uptake, and hence increased driving force for drug release. This could be retarded by the proper choice of channeling agent in order to achieve the desired zero order release profile. This system was found to deliver pseudoephedrine at a zero order rate for 12h.9
  • Liu L, Jeong K, Khang G, Lee B, Rhee JM, Lee HB prepared and evaluated the sandwiched osmotic tablet system (SOTS). The sandwiched osmotic tablet core consists of a middle push layer and two attached drug layers. Influences of tablet formulation variables, orifice size and membrane variables on nifedipine release of SOTS have been studied. It was found that potassium chloride amount of push layer and polyethylene oxide amount of drug layer had markedly positive effects on nifedipine release. A push layer /drug layer co-controlled osmotic delivery mechanism and the optimal core formulation have been proposed. The appropriate orifice size was observed in the range of 0.50–1.41 mm. It was also found that incorporating hydrophilic plasticizer in the membrane could increase the drug release rate of SOTS, whereas it decreased with hydrophobic plasticizer.10
  • Ritesh BP, Patel HR, Patel GN, Patel RP, Patel MM developed osmotic pump tablets of glipizide and optimized the formulation using response surface methodology. The complex of glipizide and HP-β-cyclodextrine were prepared and studied the effects of different ratio of drug to HP-β-cyclodextrin and preparation methods on complex formation. Response surface methodology was used to optimize the osmotic pump tablets. In-vitro drug release profiles from osmotic tablet were compared withtheoretical release profile and statistically analyzed to examine suitability of osmotic pump tablet for once a day administration. Complex prepared using solvent evaporation method in ratio of 2:1 showed good solubility and dissolution enhancement.11
  • Ramakrishna N, Mishra Bcompared the performance of cellulose acetate (CA) and ethylcellulose (EC)–HPMC combination coatings as semipermeable membranes (SPMs) for osmotic pump tablets (OPTs) of naproxen sodium (NPS) so as to deliver a constant, predetermined amount of drug in solution form over a fixed span of time, independent of external environmental conditions.12
  • Fatima SD, Mahesh N, Hasanpasha S designed controlled porosity osmotic pump containing pore forming water soluble additives in the coating membrane, which after coming in contact with water, dissolve, resulting in an in situ formation of a micro porous structure. The effect of different formulation variables, namely level of pore former (PVP), plasticizer (dibutyl phthalate) in the membrane, and membrane weight gain were studied. Drug release was inversely proportional to the membrane weight but directly related to the initial concentration of pore former (PVP) in the membrane. Drug release was independent of pH and agitational intensity, but dependent on the osmotic pressure of the release media. Based on the in vitro dissolution profile, formulation F3C1 (containing 0.5 g PVP and 1g dibutyl phthalate in coating membrane) exhibited Peppas kinetic with Fickian diffusion-controlled release mechanism with a drug release of 93.67% in 12 hours and hence it was selected as optimized formulation.13
  • Mothilal M, Damodharan N, Laksmi KS, Sharanya VB, Srikrishna T formulated andevaluated osmotic drug delivery system of metoprolol using different concentrationsof mannitol, by wet granulation technique. The tablets were coated by dip coating with cellulose acetate. Stainless steel drills pins were used to make an orifice on tablets. With increase in osmogen content and bore size rate of drug release were found to be increasing an optimum concentration of osmogen and bore size to give a zero order release was identified.14
  • Dinesh VK, Suryaprakash TN, Easwari TSformulated acarbose loaded ultra-deformable liposome gel to provide controlled release in order to minimize local side effects. Acarbose loaded ultra-deformable liposomes were evaluated for size analysis, size distribution, entrapment efficiency and In-vitro drug release characteristics. The acarbose loaded ulta-deformable liposome gel formulations 1,2 and 3 showed percentage drug entrapment of 33.33±2.2%,42.6±1.8% and 46.66±1.2% respectively.15
  • Ganesh K, Juyal V, Badoni PP formulated monolithic matrix tablet of acarbose as controlled release tablets employing Hydroxypropyl methylcellulose and Eudragit in different concentration and combination, and sustained release behavior of the fabricated tablets were investigated. Controlled released matrix tablets containing 350mg Acarbose were developed using different drug:polymers combination. Tablet prepared by direct compression method were subjected to physical characterization. Formulation was optimized on the basis of acceptable properties and in-vitro drug release.In-vitro drug release was carried out using USP Type II at 50 rpm in 900 ml of acidic dissolution medium (pH 1.2) for 1hr, followed by 900 ml alkaline dissolution medium (pH 7.4) upto 12 hr. Standard curve and withdrawal samples were analyzed in UV-Vis spectrophotometery 625nm with alkaline potassiumpermagnate as coloring agent. formulations F1, F2, F3 wherein hydroxypropylmethylcellulose K100M was employed, it was found that increasing the concentration of the polymer resulted in linearization of drug release curve and formulation F3 gave satisfactory drug release pattern. Formulations F4, F5, F6 containing Eudragit S-100 showed quite non-linearity in drug release. The drug release rate was strongly influenced by the type of polymer and concentration of polymer.16
  • Jyotsna G, Narendra PS, Praveen T designed concept of bilayer matrix tablets containing Acarbose as immediate release component using sodium starch glycolate and cross carmillose sodium as super disintegrates and Metformin hydrochloride (HCl) for sustained release by using hydroxyl propyl methyl cellulose (HPMC K 4M), (HPMC K 100) and sodium carboxyl methyl cellulose (SCMC) as the matrix forming polymer and PVPK-30 as binder.17

6.3- Objectives of the study:
Following are the objectives of proposed work-
1. To carry out preformulation study of drug.
2.To carry out drug polymer interaction by FTIR.
3.To mask the bitter taste of drug by forming β-cyclodextrin complexes.
4.To evaluate the precompressional parameter.
5.To formulateosmotically controlledoral drug delivery containing acarbose using various
polymers by suitable method.
6.To evaluate physicochemical properties of prepared formulation.
7.To carry out In-vitro drug release study of prepared formulation.
8. To carry out drug release kinetics.
9.To carry out stability study as per ICH guidelines.
Materials and Methods:
Materials:
Drug :Acarbose
Polymers:PVP, MCC, HPMC, CMC, Ethyle cellulose, Chitosan etc.
Osmogents:Sodium chloride, Magnesium sulphate, Sorbitol, Mannitol etc.
Coaters: Cellulose acetate,PEG-400, CAP, dibutyl phthalate etc.
Method of preparation:
Osmotically controlled oral tablets of acarbose prepared byControlled Porosity Osmotic Pump

7.1 SOURCE OF DATA
Review of literature from
  • Journals such as
European Journal of Pharmaceutics and Biopharmaceutics
Asian Journal of Pharmaceutical Sciences
International Journal of Pharmaceutical Research and Bio-science
Journal of Basic and Clinical Pharmacy
Journal of Pharmaceutical Science and BioscientificResearch
International Journal of Pharmacy and Pharmaceutical Sciences
Asian Journal of Biomedical and Pharmaceutical Sciences
British Journal of Clinical Pharmacy
Journal of Controlled Release
  • Internet Browsing.
  • Laboratory based studies.
7.2 METHOD OF COLLECTION OF DATA: (Including sampling procedure, if any)
  • An overview of Osmotically Controlled Oral Drug Delivery System containing Acarbose.
  • Formulation of Osmotically Controlled Oral Drug Delivery System containing Acarbose.
  • Evaluation ofOsmotically Controlled Oral Drug Delivery System containing Acarbose as follows:
Pre compression parameters5,7,8
  • Bulk density5,7,8
  • Tapped density5,7
  • Angle of repose7,8
  • Carr’s index5,7
  • Hauser’s ratio5,7
Post compression parameters7,14
  • Thickness7,14
  • Hardness7,14
  • Weight variation7,17
  • Drug content uniformity6,14
In-vitro drug release study7,14
Drug release kinetic studies7,17
Stability study as per ICH guidelines7,14

7.3 DOES THE STUDY REQUIRE ANY INVESTIGATIONS OR INTERVENTIONS TO BE CONDUCTED ON PATIENTS OR OTHER HUMANS OR ANIMALS? IF SO, PLEASE DESCRIBE BRIEFLY.
- NOT APPLICABLE
7.4 HAS ETHICAL AND CLEARANCE BEEN OBTAINED FROM INSTITUTION IN CASE OF 7.3?
- NOT APPLICABLE
8 / REFERENCES:
1)Theeuwes F, Swanson DR, Guittard, Khanna S. Osmotic delivery system for the β-adrenoreceptor antagonist metoprolol and oxprenolol: design and evaluation of systems for once daily admistration. Br J clinPharmacy 1985;19:69S-76S.
2)Babu A, Rao PM, Ratna V. Controlled porosity osmotic pump tablet. Asian J Pharmaceut Res Health Care2010;2(1):114-26.
3)Hardik P, Patel MM. Formulation and evaluation of controlled porosity osmotic drug delivery system of carvedilol phosphate. J PharmSci Bio Res 2012;2(2):77-82.
4)Tripathi KD. Essentials of Medical Pharmacology. 5thed. Jaypee Brothers Medical Publishers (P) LTD New Delhi;2003:254
5)Precose. 2011 [cited 2013 Nov 30];[4 screens]. Available from: URL:
6)Sandhya P, Hafsa S, Ayesha S, Sunitha M, Sunil R. Formulation and evaluation of controlled release osmotic tablets of glimepiride. IOSR-J.PharmBio Sci 2013;7(4):1-7.
7)Sameer S, Chandewar AV. Oral osmotic system for delivery of lornaxicam: development and In-vitro characterization. Asian J Biomed & Ph Sc 2013;3(17):14-19
8)Kanagale P, Braj LB, Mishra A, Davadra P, Kini R. Formulation and optimization of porous osmotic pump–based controlled release system of oxybutynin. AAPS PharmSci Tech 2007;8(3):E1-E7
9)Makhija SN, Vavia PR. Controlled porosity osmotic pump-based controlled release systems of pseudoephedrine I. cellulose acetate as a semi permeable membrane. J Control Release 2003;89:5-18
10)Liu L, Jeong K, Khang G, Lee B, Rhee JM, Lee HB. Nifedipine controlled delivery by sandwiched osmotic tablet system. JControl Release 2000;68(2):145-56.
11)Ritesh BP, Patel HR, Patel GN, Patel RP, Patel MM. Development of osmotically controlled drug delivery system by inclusion complex with HP-β-CD of glipizide: optimization of formulation using response surface methodology. Asian J Ph Sci2010;5(2):74-86.
12)Ramakrishna N, Mishra B. Plasticizer effect and comparative evaluation of cellulose acetate and ethylcellulose–HPMC combination coatings as semipermeable membranes for oral osmotic pumps of naproxen sodium. Drug Dev IndPharm2002;28(4):403-12.
13)Fatima SD, Mahesh N, Hasanpasha S. Formulation and evaluation of controlled porosity osmotic pump for oral delivery of ketorolac. J B ClinPh 2013;4(1):2-9.
14)Mothilal M, Damodharan N, Laksmi KS, Sharanya VB, Srikrishna T. Formulation and in-vitro evaluation of osmotic drug delivery system of metoprololsuccinate. Int J PharmPharmSci 2010;2(2):64-68.
15)Dinesh VK, Suryaprakash TN, Easwari TS. Formulation,characterization and in-vitro evaluation of acarbose loaded ultra-deformable liposome gel for effective transdermal delivery. AdvPharmacolToxicol 2010;11(1):43-46.
16)Ganesh K, Juyal V, Badoni PP. Formulation and evaluation of acarbose. Drug Invention Today 2010;2(5):264-7.
17)Jyotsna G, Narendra PS, Praveen T. Fomrulation and evaluation of bilayer matrix tablet of acarbose and metformin hydrochloride. Int JPharmresearchBio Sci 2012;1(6):123-39.
9 / SIGNATURE OF THE CANDIDATE / (ROSHAN M A)
10 / REMARKS OF THE GUIDE / The work, which is assigned to
Mr. ROSHAN is under my guidance.
11 / 11.1 NAME AND DESIGNATION OF THE GUIDE / Mr.SRIPATHY D. M.Pharm
Asst Professor
Department of pharmaceutics,
Assistant Professor,
Srinivas College of Pharmacy
Valachil, Mangalore- 574143
11.2SIGNATURE
11.3 CO-GUIDE / -NA-
11.4 SIGNATURE / -NA-
11.5 HEAD OF THE DEPARTMENT / Dr. A.R.SHABARAYAM.Pharm, Ph.D.
HOD and Principal
Department of Pharmaceutics
Srinivas College of Pharmacy,
Valachil, Mangalore-574143
11.6 SIGNATURE
12. / 12.1 REMARKS OF THE PRINCIPAL / Recommended and forwarded for favorable consideration
12.2 NAME AND SIGNATURE / Dr. A.R. SHABARAYA M.Phrm., Ph.D.
Principal and Director