Rajiv Gandhi University of Health Sciences s311
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
BANGALORE, KARNATAKA.
ANNEXURE-ΙΙ
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1. / Name of the Candidate and Address: / ELMIRA KHORRAMIA. Permanent Address:
D/O Ali khorrami
No 131/D 3rd floor 4th cross 1st main
S.T Bed layout kormangala Bangalore-560034 Karnataka.
B. Postal Address:
ELMIRA KHORRAMI
KRUPANIDHI COLLEGE OF PHARMACY,
Chikka Bellandur,
Carmelaram Post,
Varthur Hobli,
Bangalore – 560035
Karnataka.
2. / Name of the Institute: / KRUPANIDHI COLLEGE OF PHARMACY,
Chikka Bellandur,
Carmelaram Post,
Varthur Hobli,
Bangalore – 560035
Karnataka.
3. / Course of Study and subject: / Master of Pharmacy (Pharmaceutics)
4. / Date of Admission to the Course: / 08/02/2010
5. / Title of the Project:
“Enhancement of solubility and dissolution of a model BCS class II drug by solid dispersions technique”.
6.
7. / Brief Resume of the Intended work:
6.1 Need of the Study:
The formulation of poorly soluble drugs for oral delivery now presents one of the major
challenges to formulation scientists in the industry. Various formulation parameters that play a crucial role for successful formulation are aqueous solubility, stability at ambient
temperature, humidity, photo stability and compatibility with solvents and excipients etc. Of these, solubility is the most important property for developing formulations. Compounds exhibiting dissolution rate limited bioavailability are considered class II according to BCS classification. As per recent report 46% of the total NDAs filed between 1995 to 2002 were BCS class IV, while only 9% were BCS class I drugs, revealing that a majority of approved new drugs were water insoluble. There are drug candidates that have poor solubility in water but can be dissolved by suitable conventional formulation strategies which include, Co-solvents, Milling techniques, super critical processing, solid dispersions, complexation, and precipitation techniques1.
Solid dispersion is one of the most promising strategy to improve the solubility and dissolution rate of poorly water-soluble drug. By reducing the drug particle size to the absolute minimum, solid dispersions improve drug wettability, bioavailability. They are usually presented as amorphous products. Recently, surfactant have been included to stabilize the formulation; thus avoiding drug recrystallization, thereby potentiating their solubility. The term solid dispersion has been utilized to describe a family of dosage form, whereby the drug is dispersed in a biological inert matrix, usually with a view in order to enhance the oral bioavailability. More Specifically, Chiou and Regelman (1971), define these system as ‘the dispersion of one or more active ingredient in an inert matrix at solid-state prepared by the melting (fusion), solvent or melting solvent method2.
The development of solid dispersions is a practically viable method to enhance bioavailability of poorly water-soluble drugs overcomes the limitations of previous approaches such as salt formation, solubilization by cosolvents, and particle size reduction. Studies revealed that drugs in solid dispersion need not necessarily exist in the micronized state. A fraction of the drug might molecularly disperse in the matrix, thereby forming a solid dispersion3.
When the solid dispersion is exposed to aqueous media, the carrier dissolves and the drug releases as fine colloidal particles. The resulting enhanced surface area produces higher dissolution rate and bioavailability of poorly water-soluble drugs. In addition, in solid dispersions, a portion of drug dissolves immediately to saturate the gastrointestinal tract fluid, and excess drug precipitates as fine colloidal particles or oily globules of submicron size.
The proposed project is focussing on enhancing the solubility and dissolution of a model BCS Class II drug to overcome poor bioavailability.
6.2 Main Objective of the Study:
Broadly, the work would endeavor to achieve the following objectives;
Ø Selection of a model BCS Class II drug based on pharmacokinetic parameter suitable for formulation and evaluation of solid dispersion
Ø Selection of appropriate carriers like polyvinyl pyrrolidone and polyethylene glycol etc suitable for formulating solid dispersions.
Ø Conducting preformulation studies about the drug and excipients using FTIR, DSC techniques.
Ø Formulation of solid dispersions using selected carriers.
Ø Evaluation of formulations using FTIR, DSC and invitro drug release studies etc.
Ø Comparison of dissolution profiles of the pure drug with formulated solid dispersion.
Ø Conducting stability studies for the optimized formulation.
6.2 Review of Literature:
Suporn Charumanee et al., have reported the advantages and limitations and practical applicability of surface solid dispersion over other techniques. The authors were successful in improving the dissolution rate of piroxicam by surface solid dispersion4.
K.P.R.Chowdary et al., reported prepration and evaluation of solid dispersion of meloxicam in polyvinyl pyrrolidone, hydroxy propyl methyl cellulose, hydroxy propyl cellulose and poly ethylene glycol and solvent deposited system. On lactose, soluble starch, microcrystalline cellulose, dicalcium phosphate, silica gel. A marked enhancement in dissolution rate and dissolution efficiency of meloxicam was observed with all solid dispersion and solid deposited systems. The solvent deposited system on carriers could be formulated to tablets. These tablets, apart from fulfilling the official and other specifications, exhibited higher rates of dissolution and dissolution efficiency values5.
V.Ganesn et al., reported enhancement in dissolution rate of flurbiprofen by solid dispersion of flurbiprofen in polyvinyl pyrrrolidone, HPMC, HPLC and PEG and deposited system on lactose, soluble starch, MCC, DCP, silica gel6.
Siavoush Dastmalchi et al., showed that solvent deposition technique was an effective tool for increasing dissolution, probably due to enhanced wettability and reduced drug particles size. The drug solid dispersion prepared by solvent deposition technique using micro crystalline cellulose had the carrier in different ratios and their dissolution rates were
compared to those of pure drug and its physical mixture with carrier7.
Noriyuki Hirasawa et al, reported a method to prepare solid surface dispersion granules by granulation method using high-speed agitation granulator at the rate of 600 rpm with an agitator and 2400 rpm with chopper8.
Adrian C. Williams et al., reported different method for preparation of solid dispersion techniques like hot mix method, co grinding, co precipitation and solvent deposition method for Ibuprofen. The increased dissolution rate could be attributed to a combination of faster dissolution from amorphous drug Ibuprofen, microcrystalline drug deposited on the carrier surfaces and polymer swelling9.
R.P. Dixit et al., have reported the invitro and invivo advantages of surface solid dispersion of celecoxib on super disintegrants. The technique provided an improvement in bioavailability of the drug10.
K.P.R. Chowardy et al., investigated surface solid dispersions of itraconazole in lactose, microcrystalline cellulose and three super disintegrating agents and their formulation into tablets with an objective of enhancing the dissolution rate of drug from tablet formulation. Solid dispersion in super disintegrating agents gave much higher rates of dissolution than the dispersions in other excipients11.
K.Venkates Kumar et al., reported the improvement of solubility and dissolution behaviour of the poorly soluble drug, valsartan by solid dispersion technique using SMP(skimmed milk powder) as carrier12.
Punitha S et al., have reported the enhancement of solubility and dissolution of celecoxib by solid dispersion technique. The solubility and dissolution studies showed there is a possibility of improvement solubility of celecoxib through solid dispersion with Urea13.
Neelam Seedhar et al., have reported micellar solubilization of some poorly soluble anti diabetic drug such as glipizide, pioglitazone, glyburide and gliclazide using cationic(CTAB) anionic(SDS) and non-ionic (tween 80) surfactants and cationic-nonionic and anionic-nonionic surfactant mixture in the absence and presence of salt (0.15M NaCl) or phosphate buffer (0.1 M pH7.4)14.
D Choudhary et al., reported dissolution rate of glipizide was increased from solid dispersion prepared by the kneading technique by using poloxamers without any physical and chemical interaction2.
Materials and Methods:
Drug: BCS Class II drug
Materials: Poly vinyl pyrrolidine, PEG 4000, Poloxamer 407 etc.
7.1 Source of Data:
Preliminary data required for the experimental study would be obtained from,
1. Krupanidhi College of Pharmacy library.
2. Scientific Journals.
3. Pubmed, Science Direct & other internet resources.
7.2 Method of Collection of Data (including sampling procedure, if any):
The physicochemical properties, of the drug will be collected from drug information center, various standard Books, journals, websites and other sources like research literature bases data such as Medline, Science Direct etc.
The experimental data will be collected from study of the drug; its formulation, through investigation of the process and product variables in the laboratory of Krupanidhi College of Pharmacy, Bangalore-35, following pharmacopoeial and standard methodologies.
The steps involved in such studies are given as under :
Ø Selection of a model BCS Class II drug based on pharmacokinetic parameter suitable for formulation and evaluation of solid dispersion
Ø Selection of appropriate carriers like polyvinyl pyrrolidone and polyethylene glycol etc suitable for formulating solid dispersions.
Ø Conducting preformulation studies about the drug and excipients using FTIR, DSC techniques.
Ø Formulation of solid dispersions using selected carriers.
Ø Evaluation of formulations using FTIR, DSC and invitro drug release studies etc.
Ø Comparison of dissolution profiles of the pure drug with formulation solid dispersion.
Ø Conducting stability studies for the optimized formulation.
7.3 Does the study require any investigations of interventions to be conducted on
Patients or other human or animals? If so please describe briefly?
Not applicable.
7.4 Has ethical clearance been obtained from your institute in case of as above?
Not applicable.
8. / List of References:
1) Venkate Kumar K, Arunkumar N, Verma PRP, Rani C. Preparation and in vitro characterization of valsartan solid dispersion using skimmed milk powder as carrier. Int J Pharm Res 2009 July-Sept; 1(3):431-7.
2) Choudhary D, Kumar S, Gupta GD. Enhancement of solubility and dissolution of glipizide by solid dispersion(kneading) technique. Asian J Pharm 2009;3(3):245-51.
3) Rahul Ghaste, Dhanyakumar DC, Rohit R, Dhananjay S. Solid dispersion. A review (Online) 2009 [cited 2010Nov 22]; Available from: URL: http://www.Pharmainfo.net.
4) Suporn Charumanee, Siriporn Okonoki and Jakkapan Sirithunyalug. Improvement of dissolution rate of piroxicam by surface solid dispersions. CMU J 2004;3(2):77-84.
5) Chowdary KPR and Hymavathi R. Enhancement of dissolution rate of meloxicam. Ind J Pharm Sci 2001 Mar-Apr; 63(2):154-5.
6) Ganesan V, Shiva kumar SM and Kannadasan M. Enhancement of dissolution rate of flurbiprofen. Ind Pharmacist 2004Mar; 3:61-4.
7) Siavoush dastmalchi, Alireza garjani, Nasrin maleki, Golaleh sheikhee, Vida baghchevan, Parisa jafari-azad et al. Enhancing dissolution, serum concentration and hypoglycemic effect of glibenclamide using solvent deposition technique. Int J Pharm Sci 2005;8(2):184-90.
8) Noriyuki Hirasawa, Sayoko Ishise, Hitomi Miyata and Azzumi Danjo. Application of nivaldipine solid dispersion to tablet formulation and manufacturing using crospovidone and methylcellulose as dispersion carriers. Chem Pharm Bull 2004;52(2):244-7.
9) Adrian C, Peter Timins, Mingchu Lu, Robert T. Disorder and dissolution enhancement, deposition of ibuprofen onto insoluble polymers. Eur J Pharm Sci 2005;26:288-94.
10) Dixit RP and Nagarsenker MS. In vitro and in vivo advantage of celecoxib surface solid dispersion and dosage form development. Ind J of Pharm Sci 2007 May-June; 69(3):370-7.
11) Chowdary KPR and Srinivasa Rao SK. Investigation of dissolution enhancement of itraconazole by solid dispersion in super disintegration. Drug Development and Industrial Pharmacy 2000;26(11):1207-11.
12) Venkate Kumar K, Arunkumar N, Verma PRP, Rani C. Preparation and in vitro characterization of valsartan solid dispersion using skimmed milk powder as carrier. Int J Pharm Res 2009;1(3):431-7.
13) Punitha S, Kathikeyan D, Devi P and Vedha Hari BN. Enhancement of solubility and dissolution of celecoxib by solid dispersion technique. J Pharm Sci 2009;1(2):63-8.
14) Neelam Seedhar and Mamta Kanojia. Micellar solubilization of some poorly soluble anti diabetic drug. Pharmatech Sci 2008 June; 9(2):431-6.
9. / Signature of the Candidate: / (ELMIRA KHORRAMI)
10. / Remarks of the Guide:
Over the years, a variety of solubilization techniques have been studied and widely used, by many estimates up to 40 per cent of new chemical entities discovered by the pharmaceutical industry today are poorly soluble or lipophilic compounds. The solubility issues complicating the delivery of these new drugs also affect the delivery of many existing drugs. The various techniques are available for enhancement of solubility. Solid dispersion is one of the most promising approach for solubility enhancement and having a potential for commercial application. So we recommend for necessary clearance.
11. / Name and Designation of
11.1 Guide: / Mrs. BHARANI S SOGALI
ASSISTANT PROFESSOR,
Department of Pharmaceutics
Krupanidhi College of Pharmacy,
Bangalore-35.
11.2 Signature of Guide:
11.3 Co-Guide:
11.4 Signature of co-Guide:
. / 11.5 Head of Department: / Prof. Dr. R.S. THAKUR
PROFESSOR AND HEAD
Department of Pharmaceutics
Krupanidhi College of Pharmacy,
Bangalore-35.
11.6 Signature of HOD:
12. / 12.1 Remarks of the Principal:
12.2 Signature of Principal: / Dr. N PREM KUMAR
PRINCIPAL
Krupanidhi College of Pharmacy,
Chikka Bellandur,
Carmelaram Post,
Varthur Hobli,
Bangalore – 560035.
Dept of Pharmaceutics, KCP, Bangalore. Page 5