RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

BANGALORE, KARNATAKA

ANNEXURE- II

PROFORMA FOR REGISTRATION OF SUBJECT FOR

DISSERTATION

1. / Name of the Candidate and Address: / MOHAN KUMAR.V
#317 ,9th main,
Prashanthnagar, Vijaynagar,
Bangalore-560079
2. / Name of the Institute: / Government College of Pharmacy,
Bangalore - 560027
3. / Course of Study and Subject: /

Master of Pharmacy in Pharmaceutics

4. / Date of admission to course /
25 JULY 2011
5. / Title of the topic :
“SOLUBILITY ENHANCEMENT OF A POORLY WATER SOLUBLE MODEL ANTI- HYPERTENSIVE DRUG”
6. / Brief Resume of Intended Work:
6.1: Need for the Study:
Ø  Hypertension is multifaceted, insidious disorder associated with cardiovascular cerebral and renal vascular abnormalities.
Ø  A number of oral antihypertensive drugs have been developed in order to improve bioavailability.
Ø  Calcium channel blockers are widely used in the treatment of hypertension, and enhancement of dissolution rates of water insoluble drugs remains one of the most challenging tasks of drug development.
Ø  Solubility enhancement is important approach to improve the bioavailability of drugs.
Ø  This is an attempt to enhance solubility of a model anti hypertensive drug by using hydrophilic binders.
Ø  Another important technique to enhance solubility is solid dispersion, which was developed by Chiou and Reigelman; this may result in improved solubility and dissolution rates as compared with crystalline material.
Ø  Improving bioavailability of drug those given as solid dosage forms remains a great challenge for the formulation scientists, so this is an attempt to increase the solubility and bioavailability of poorly water soluble anti hypertensive drug.
6.2: Review of literature

1. V K Rai, Brajendra Singh Rajput, Manoj Sharma, Ashish Agarwal, Anil Gupta,and Narendra Singh.,Studied the enhancement of dissolution of a poorly soluble drug, Raloxifene Hydrochloride (RLX-HCl), using solid oral dosage form.Solubility study for pure drug was done in different relevant media, which results in poor solubility of drugs. Hydrophilic binders likePolyvinylpyrrolidone, Hydroxy propyl methyl Cellulose, Hydroxypropyl cellulose were investigated for the purpose to improve the solubility in the formulation. Comparison was made with Hydrophobic binder viz Ethyl cellulose. Dissolution behavior of different formulation and pure drug was studied in different relevant media, which reveals significant improvement in dissolution behavior of drug with hydrophilic binder5.

2. Vijay Kumar, M M Shankaraiah, J S Venkatesh, D Rangaraju, C Nagesh., Studied the solid dispersion of poorly water soluble drug Fenbendazole as a model drug. The purpose of this study was to enhance the dissolution of fenbendazole by solid dispersions consisting of the drug,and a polymeric carrier ,Binary and ternary system were prepared by kneading method using hydrophilic polymers like polyvinylpyrrolidine K-25( PVP-K25),beta-cyclodextrin (BCD), mannitol and urea.
The prepared formulations were charecterised by polymer compatibility by using FT-IR and the drug content uniformity was found to be good in all formulations. The solubility of Fenbedazole were greater with fenbendazole-BCD-PVP K25 system. Dissolution rates of fenbendazole were significantly increased by binary and ternary system. The result confirmed that ternary system showed better solubility and dissolution characteristics when compared to binary system8.

3. Bhanudas Shankar Kuchekar, Minal Raghunath Narkhede., Studied the effect of the presence of the water soluble polymers like HPMC, PVP and PEG 6000 on aqueous solubility and complexation abilities felodipine with or without presence of β-cyclodextrin and HPβCD by phase solubility studies. Addition of water soluble polymer to βCD solution improved βCD solubilizing efficiency due to increase in βCD complexing power toward felodipine. In binary system solubility was found to be 2.5 to 10 times higher than in water which was further improved in the presence of 0.25% w/v water soluble polymer. Ternary systems with βCD showed highest increments in solubility towards felodipine, with 78.8%, 81.8% and 74% improvement after the addition of 0.25% w/v HPMC, PVP and PEG6000 , respectively. All the polymers under study showed synergistic effect on felodipine cyclodextrin solublization by increasing complexation efficiency. The highest solubility improvement up to 81.8% was obtained for ternary system when 0.25% w/v of PVP was used3.

4. V P Patel, M C Gohel, R K Parikh, Studied about the increase dissolution rate of felodipine by complexation process. Complexes were prepared using cyclodextrin by employing various techniques like physical mixture, cogrinding, kneading technology, solvent coevaporation.

The physical properties of the prepared solid mass of FDP was characterized by in vitro dissolution studies, UV- spectroscopy, FT-IR, DSC and X-ray powder differaction spectroscopy. Additionaly, phase solubility studies were performed to support the in vitro dissolution study. The results of Fourior transform infrared spectroscopy shows the compatibility of drug with cyclodextrin, while differential scanning calorimetry (DSC) and X-ray powder differaction spectroscopy showed the confirmation of complexation of cyclodextrin with felodipine9.

5. Dong-Han Won, Min-Soo Kim, Sibeum Lee, Jeong-Sook Park, Sung-Joo Hwang.,Prepared Solid dispersions of felodipine with HPMC and surfactants by the conventional solvent evaporation (CSE) and supercritical anti-solvent precipitation (SAS) methods. The solid dispersion particles were characterized by particle size, zeta potential, SEM, DSC, powder X-ray diffraction (XRD), solubility and dissolution studies. The effects of the drug/polymer ratio and surfactants on the solubility of felodipine were also studied. , the particle sizes of solid dispersions from the SAS process were maintained for 6 h due to the increased solubility of felodipine. The physical state of felodipine changed from crystalline to amorphous during the CSE and SAS processes, confirmed by DSC/XRD data2.

6. K P R Chowdary, K Surya Prakasa Rao and Udaya Sree Datla.,

Studied the individual and combined effects of hydroxy propyl β cyclodextrin (HPβCD), surfactant (Poloxamer 407) on the solubility and dissolution rate of piroxicam, a BCS class II drug in a series of 22 factorial experiments. The solubility of piroxicam in four selected fluids containing HPβCD and Poloxamer 407 as per a 22 factorial study was determined. HPβCD and Poloxamer 407 alone gave an increase of 1.55 and 1.86 fold respectively in the solubility of piroxicam in combination they gave only 1.33 fold increase
in the solubility of piroxicam. Combination of HPβCD with Poloxamer 407 gave much higher enhancement in the dissolution rate and efficiency (DE30) of piroxicam than is possible with them individually. Hence a combination of HPβCD and Poloxamer 407 is recommended to enhance the dissolution rate of piroxicam10.

7. Tao Taoa, Yan Zhaoa, JinjinWua, Beiyi Zhoub., have prepared and evaluated itraconazole dihydrochloride for solubility and dissolution rate enhancement. Itraconazole dihydrochloride was synthesized by bubbling anhydrous hydrogen chloride gas into acetone suspension of itraconazole. Its structure was confirmed by FT-IR, TGA, DSC, powder X-ray diffraction, SEM and Dynamic light scattering. It is concluded that hydrochloride formation increases solubility with beta cyclo dextrin(1/3)1.

.

8. S Muralidhar, G Devala Rao, Syed Azhar,Nizami, Karunakara reddy, S Ravindra reddy., Studied about solid dispersions, which were prepared in differentproportions using hydrophilic carriers like polyethylene glycol 6000 and poly vinyl pyrrolidone K30. The differential scanning calorimetry (DSC) thermograms and infrared (IR) spectra revealed that there was nointeraction of celecoxib with additives and no degradation in celecoxib molecule. The drug release profile was studied in water containing 2% SLS, solid dispersions exhibited superior dissolution profile and improved anti-inflammatory activity in rat paw oedema model. The increase in the dissolution rate and consequent enhancement of anti-inflammatory effect of celecoxib in rats were attributed to wettability, solubilization of the drug by the carriers and possibility due to reduction in the particle size6.

9. Renu Kalyanwat, Stuti Gupta, Rajendra Kr Songara, Dolly Jain and Sushma Patel., Studied about enhancement of dissolution rate of carbamazepine by solid dispersion. This solid dispersion of carbamazepine was prepared by modified solvent evaporation method. Two types of superdisintegrants croscarmellose sodium and sodium starch glycolate were incorporated. Different batches of solid dispersion were prepared and evaluated by drug content determination, saturation solubility study and dissolution study. Thus dissolution rate of carbamazepine was found to be increased with super disintegrant addition11

.
10. Jessy Shaji , Digambar Jadhav., They studied about development of solid dispersion self emulsification pellets (SDSEP). This is a recent technique for poorly water soluble drugs, where it increases water solubility and enhances the bioavailability. A full factorial design approach was used for the optimization of MCC: Lactose (X1) and % of croscarmellose sodium (X2) were taken as an independent variable. Cumulative % drug release (Y1), Disintegration Time (Y2) and Friability (Y3) were studied as response variables. The differential scanning calorimetry and x-ray diffraction studies demonstrated that enhanced dissolution of Ibuprofen from SDSEP might be due to a decrease in the crystallinity of IBU. In conclusion, dissolution enhancement of Ibuprofen was obtained by preparing a solid dispersion self emulsion using melt technique. The use of a factorial design approach helped in identifying the critical factors in the preparation and formulation of SDSE7
.

11.V K Rai, N Pathak, N Bhaskar, B C Nandi, S Dey, L K Tyagi.,

They studied about Raloxifene HCL immediate release tablets by wet granulation technique, in order to obtain the best, optimized 6 different formulation were developed.
Different fillers, binders, lubricants were taken as variables. Evaluation of tablets was studied as response variables.
Sticking was observed in the formulation containing stearic acid and sodium stearyl fumerate.The different physical properties and in vitro release profile showed best comparable with reference product4.
6.3:Main objective of the study:
The present work is an attempt to,
*Enhancing the dissolution rate or solubility in vivo by using hydrophilic binders in different gastrointestinal fluids and also by solid dispersion in
solid dosage form by the one of the following method ;
·  Kneading method
·  Solvent evaporation method
·  Fusion method
·  Wet granulation
Evaluation of the formulation
·  Drug-polymer incompatibility studies
·  Drug content .
·  Uniformity of weight
·  Friability and Hardness
·  Disintegration time
·  Stability studies
·  Dissolution studies.
v  Characterization of Solid dispersion :
·  FT-IR
·  DSC
·  X-Ray Diffraction
Materials & methods :
Drug: Calcium Channel Blockers (Felodipine)
,
Polymers used : Hydroxypropyl methyl cellulose, Hydroxypropyl cellulose, Polyvinyl pyrolidine, Ethyl cellulose, etc..,
7.1 Source of the data :
The data required for the work will be collected from different books , Journals and articles available in the Library of Govt. college of Pharmacy, Journals available at Jgate – Helinet of the Rajiv Gandhi University of Health Sciences, website and through various internet sources.
7.2 Method of collection of data:
The data will be collected from the designed formulation, then subjecting the formulation to different studies like, invitro drug release studies, drug content, drug polymer compatibility studies, general appearance, size, shape, tablet thickness, hardness, friability, stability studies, on the selected formulation and other tests as necessary during the evaluation part of formulation.
7.3 Does the study require any investigations or interventions to be
Conducted on patients or other humans or animals? If so, please
describe in brief.
“Not applicable”
7.4 Has ethical clearance been obtained from your institute in case 7.3?
“Not applicable”
8. List of references:
1. Tao Taoa, Yan Zhaoa, JinjinWua, Beiyi Zhoub; Preparation and evaluation of Itraconazole dihydrochloride for the solubility and dissolution rate enhancement; International journal of Pharmaceutics;2009;367;109-114.
2. Dang Han won, Min soo kim, Sibuem lee, Jeong sook park Sung joo Hong; Improved physicochemical characteristics of felodipine solid dispersion particles by super critical anti- solvent precipitation process. IIJ.Pharm;2005(;1-2);199-208.
3. Bhanudas Shankar Kuchekar, Minal Raghunath Narkhede., The effect of water soluble polymers on Felidipine solubility and complexing abilities with modified cyclodextrin. Iranian journal of pharmaceutical sciences. 2007;3(4);197-202.
4. Rai V.K, Pathak.N, Bhaskar.R, Nandi.B.C, Dey.S, Tyagi.L.K; Optimization of immediate Release tablet of Raloxifene hydrochloride by wet
granulation method; International journal of pharmaceutical sciences and drug research; 2009;1(1);51-54
5. V K Rai, Singh Rajput, Manoj Sharma, Ashish Agarwal, Anil Gupta and Narendra Singh,; Solubility enhancement of poorly water soluble drug using different Hydrophillic binders in solid dosage form; International journal of comprehensive pharmacy;2010;3;05.
6. S Muralidhar, G Devala Rao, Syed Azhar Nizami, Karunakara reddy, S.Ravindra Reddy; Enhancement of dissolution rate and anti inflammatory potential of celecoxib using solid dispersion; journal of advanced pharmaceutical research; 2010;1;74-81.
7. Jessy Shaji , Digambar Jadhav; Statistical developement and optimization of solid dispersion self Emulsifying Pellets; International journal of pharmaceutical sciences;2010;4(3);156-167.
8. Vijay Kumar, M M Shankaraia, J S Venkatesh, D Rangaraju , C.Nagesh, Characterization of ternary system poorly soluble drugs in various Hydrophilic carriers International research journal of pharmacy; 2011;2;143-145.
9. V P Patel, M C Gohel, R K Parikh, Invitro Dissolution enhacement of Felodipine bu using cyclo dextrin; Indo-Global Journal of pharmaceutical sciences;2011;1(2);194-205.
10. K P R Chowdary, K Surya prakash rao, and Udaya Sree Datla; A Factorial study on the effects of hydroxyl propyl beta cyclodextrin and Poloxamer on the solubility and dissolution rate of piroxicam; International journal of advances in pharmaceutical research; 2011;2(8);412-417.
11. Renu Kalyanwat, Stuti Gupta, K R Rajendra Songara, Dolly Jain and Sushma Patel; Study of enhancement of dissolution rate of carbamazipine by solid dispertion technique; International journal of comprehensive pharmacy;2011;5(09);1-4.
Signature of the Candidate: /
(MOHAN KUMAR.V.)
Remarks of the Guide:
Name and Designation of:
11.1 Guide:
11.2 Signature: / Mrs. MANJULA. B. P.,
ASST. PROFESSOR,
DEPT. OF PHARMACEUTICS,
GOVT. COLLEGE OF PHARMACY,
BANGALORE – 560027
11.3 Co-Guide:
11.4 Signature: / NOT APPLICABLE
NOT APPLICABLE
11.5 Head of the Department:
11.6: Signature: / Dr N. G. NANJUNDASWAMY,
PROFESSOR,
DEPT. OF PHARMACEUTICS,
GOVT. COLLEGE OF PHARMACY,
BANGALORE- 560027
12.1 Remarks of the Chairman and Principal:
12.2 Signature:
Dr. S. SHASHIDHARA,
PRINCIPAL,
GOVT. COLLEGE OF PHARMACY,
BANGALORE – 560027