RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, …



RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA, BANGALORE.

[pic]

M. PHARM SYNOPSIS

YEAR OF ADMISSION-NOVEMBER 2010

TITLE OF THE SYNOPSIS

“FORMULATION AND EVALUATION OF LIQUISOLID TABLET OF NON STEROIDAL ANTI-INFLAMMATORY DRUGS”

BY

MOHAN DHONDIRAM DHERE

(M. PHARM)

DEPARTMENT OF PHARMACEUTICS

UNDER THE GUIDANCE OF

PROF. SIDHARTH M PATIL

DEPARTMENT OF PHARMACEUTICS

[pic]

KLES’s COLLEGE OF PHARMACY

AKKOL ROAD, NIPANI

KARNATAKA

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES KARNATAKA, BANGALORE.

ANNEXURE-II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

| | | |

|1. |NAME OF THE CANDIDATE |Mr. MOHAN DHONDIRAM DHERE |

| |AND ADDRESS |S/o.- DHONDIRAM DADU DHERE |

| | |A/P. - NIPANI |

| | |DIST. - BELGAUM |

| | |PIN CODE - 591237 |

| | |STATE - KARNATAKA |

| | | |

| | | |

|2. |NAME OF THE INSTITUTION |KLES’s COLLEGE OF PHARMACY |

| | |AKKOL ROAD,NIPANI |

| | |DIST:- BELGAUM |

| | |KARNATAKA. |

| | | |

| | | |

| | | |

| | | |

|3. |COURSE OF STUDY AND SUBJECT |MASTER OF PHARMACY IN PHARMACEUTICS |

| | | |

| | | |

| | | |

| | | |

| | | |

|4. |DATE OF ADMISSION |6 AUGUST 2010 |

| | | |

| | | |

| | | |

| | | |

| | | |

| | | |

|5. |TITLE OF THE TOPIC |“FORMULATION AND EVALUATION OF LIQUISOLID TABLET OF NON STEROIDAL ANTI-INFLAMMATORY DRUGS” |

| | |

|6 |BRIEF REVIEW OF THE INTENDED WORK |

| | |

| |1) Need for the study |

| | |

| |The poor dissolution rate of water insoluble drugs is still a substantial problem confronting the pharmaceutical industry. A great number of|

| |new and, possibly, beneficial chemical entities do not reach the market merely because of their poor oral bioavailability due to inadequate |

| |dissolution. Over the years, various solid dosage formulation techniques to enhance the dissolution of poorly soluble substances have been |

| |introduced with different degrees of success. The technique of ‘liquisolid compacts’ is a new and promising addition towards such a novel |

| |aim .1 |

| |It is well established that the active ingredient in a solid dosage form must undergo dissolution in order to become available for |

| |absorption from the gastrointestinal tract. The absorption rate of a poorly water-soluble drug, formulated as an orally administered solid |

| |dosage form, is controlled by its dissolution rate in the fluid present at the absorption site, i.e. the dissolution rate is often the |

| |rate-determining step in drug absorption .2 |

| |Liquisolid technique is a new and promising method that can change the dissolution rate of drugs. It has been used to enhance dissolution |

| |rate of poorly water-soluble drugs. |

| |For poorly soluble and highly permeable (Class II) drugs, the rate of oral absorption is often controlled by the dissolution rate in the |

| |gastrointestinal tract. Therefore, together with the permeability, the solubility and dissolution behavior of a drug are key determinants of|

| |its oral bioavailability. 3 |

| |These drugs are defined as those with high permeability but whose solubility in aqueous media is not sufficient for the whole dose to be |

| |dissolved in the gastrointestinal tract. For these substances dissolution is therefore the rate determining step to absorption. 4 |

| |In this study one of the available non steroidal anti- inflammatory drugs will be selected as model drug, which is sparingly soluble in |

| |water. Based on the Biopharmaceutics Classification System (BCS), it is classified as a Class II drug. Selected drug will be fabricated as |

| |liquisolid tablet and will be evaluated. |

| | |

| |2) - Review of Literature |

| |1) Literature review on liquisolid compacts |

| |1. Darwish IM et al. studied the dissolution enhancement of glibenclamide using liquisolid tablet technology. The effect of the powder |

| |substrate composition and the volume of the added liquid on the flowability and compressibility of the final mixture are studied. In |

| |addition, the effect of the type of the coating material and drug concentration on the dissolution pattern of glibenclamide formulated in |

| |liquisolid tablets were investigated. Liquisolid tablets exhibited a superior in vitro release pattern compared to that of marketed |

| |products. Based on the work presented in this paper, the higher dissolution rates displayed by the liquisolid tablets may also enhanced |

| |oral bioavailability of glibenclamide .5 |

| | |

| |2. Patel VP et al., have carried out dissolution enhancement of glipizide using liquisolid tablet technology. Use of liquisolid systems to |

| |improve the dissolution property of water-insoluble agents was investigated using drug glipizide a. It is included that the type of coating |

| |material used affects the flowability and compressibility of the final admixture. There is no any effect on glipizide dissolution rate. Low |

| |R values displayed relatively poor dissolution properties and increased Lf values resulted in a marked decrease in the compressibility of |

| |final mixture. 6 |

| | |

| |3. Fahmy RH et al., (2008) studied the enhancement of famotidine dissolution rate through liquisolid tablet formulation. The need of study |

| |was to improve famotidine dissolution rate through its formulation into liquisolid systems and then to investigate the in vitro performance |

| |of the prepared liquisolid tablets. Both DSC and XRD suggested loss of famotidine crystallinity upon liquisolid formulation which was |

| |further confirmed by SEM indicating that even though the drug existed in a solid dosage form, it is carried within the powder substrate in a|

| |solubilized and molecularly dispersed state, which contributed to the enhanced drug dissolution properties All the tested liquisolid tablet |

| |formulations shows high drug dissolution rates than the conventional and directly compressed tablets. 7 |

| | |

| | |

| | |

| | |

| |4. Spireas S et al., (1998) evaluated in vitro release patterns of hydrocortisone liquisolid tablets. The in vitro release patterns of this |

| |slightly water soluble corticosteroid, formulated in directly compressed tablets and liquisolid compacts , are studied at different |

| |dissolution conditions. The in vitro drug dissolution rates of liquisolid tablets were found to be consistent and independent of the volume |

| |of dissolution medium used, in contrast to the plain tablets, which exhibited declining drug release patterns with decreasing dissolution |

| |volumes .8 |

| | |

| |5. Spiras S et al., (1999) demonstrated the effect of powder substrate on the dissolution property of methylclothiazide liquisolid compacts.|

| |Enhanced release profiles may be exhibited by such systems due to the increased wetting properties and surface of drug available for |

| |dissolution. It was observed that maximum drug release rate can be exhibited by systems that have powder substrates with optimum carrier to |

| |coating ratios. In addition, liquisolid tablets displayed significantly enhanced dissolution profiles compared to those of marketed |

| |products.9 |

| | |

| |6. Spireas S et al., (1998) studied the enhancement of prednisolone dissolution properties using liquisolid compacts. In this study, the |

| |potential of liquisolid systems to improve dissolution properties of water insoluble agents was investigated using prednisolone as the model|

| |drug. The new technique of liquisolid compacts appears to be a promising alternative for the formulation of water insoluble drugs, such as |

| |prednisolone, into rapid release tablets, which may present improved oral bioavailability. Liquisolid compacts demonstrated significantly |

| |higher drug release rates, in different dissolution media and volumes, compared to tablet prepared by the direct compression method .10 |

| | |

| |7. Javadzadeh Y et al., evaluated the effects of different grades of microcrystalline cellulose on flowability, compressibility and |

| |dissolution of liquisolid systems. The results showed that among the evaluated different grades of MCC, compacts containing MCC PH 101 and |

| |102 showed better dissolution profiles. Microcrystalline cellulose PH 101 was found to be a suitable carrier for having acceptable |

| |flowability, friability, hardness, and dissolution profile .11 |

| | |

| | |

| | |

| | |

| |8. Javadzadeh Y et al., (2007) designed liquisolid technique for dissolution rate enhancement of a high dose water insoluble drug |

| |carbamazepine. In order to reduce the amount of carrier in liquisolid formulations, some additives namely polyvinyl pyrolidone (PVP), HPMC, |

| |PEG (35000) were added to liquid medication to increase loading factor. The effect of various ratios of carrier to coating material, PVP |

| |concentration, effect of aging and type of carrier on dissolution rate of liquisolid compacts was studied. It was shown that MCC had more |

| |liquid retention potential in comparison with lactose and formulation containing MCC as a carrier, showed higher dissolution rate .12 |

| | |

| |9. Javadzadeh Y et al., (2005) studied enhancement of dissolution rate of piroxicam using liquisolid compacts. In this study, the |

| |dissolution behaviors of piroxicam from liquisolid compacts was investigated in simulated gastric fluid (SGF, pH 1.2)and simulated |

| |intestinal fluid (SIF, pH 7.2).The results showed that liquisolid compacts demonstrated significantly higher drug release rate than those of|

| |conventionally made .13 |

| | |

| |10. Rakshit P et al., designed formulation and evaluation of liquisolid compacts of piroxicam. Several formulations of liquisolid compacts |

| |containing various ratios of drug: dissolution enhancing agent (tween 80, PEG 400, PG) ranging from 1:1,1:3,1:5,1:7,1:9 were prepared. |

| |Piroxicam: tween 80 (1:3) ratios showed highest solubility and faster dissolution. It is shown that the surfactant like tween 80 or |

| |combination of tween 80 and SLS could be economic substitute as a dissolution enhancing agent .14 |

| | |

| |11. Tayel SA et al., (2008) developed a method for improvement of dissolution properties of carbamazepine through application of the |

| |liquisolid tablet technique. Reported liquid load factors, and excipients ratio were used to calculate the required amounts of excipients |

| |necessary to prepare the compacts or tablets according to a mathematical model. The wettability of carbamazepine was improved by making a |

| |suspension in PG, the water soluble, nonvolatile liquid. A liquid load factor Lf = 0.25, and excipients ratio R = 20, produced a powder of |

| |optimal flow properties and readily compressible into tablets without any liquid phenomenon. 15. |

| | |

| | |

| | |

| |3) - Objective of the Study |

| |Following are the objectives of the present study |

| | |

| |To formulate liquisolid compacts of non steroidal anti- inflammatory drug. |

| |To evaluate liquisolid compacts of non steroidal anti- inflammatory drug. |

| |To enhance the dissolution rate of poorly water-soluble drugs using liquisolid technique. |

| |To assess effect of adjuvant on the performance of liquisolid compacts. |

| |To perform stability studies as per ICH guidelines. |

| | |

| | |

| | |

| | |

| | |

| | |

| | |

| | |

| | |

| | |

| | |

| | |

| | |

| | |

| | |

| | |

| | |

| | |

| | |

| | |

| |MATERIALS AND METHODS |

|7.0 |Materials under consideration:- |

| |APIs- One of the NSAID candidate from class II category of BCS classification. |

| |Excipients:- |

| |Microcrystalline cellulose (Avicel PH 102) |

| |silicon dioxide (Avicel 200) |

| |Sodium starch glycolate |

| |Propylene glycol |

| |Method:- |

| |Preformulation studies will be performed so as to assess interaction between drug and excepients. |

| | |

| |Method of preparation: |

| |In present study any of the reported method will be used for preparation of Liquisolid tablets. |

| | |

| |Evaluation methods : |

| | |

| |Evaluation of Liquisolid Compacts: |

| | |

| |Percentage Yield |

| |Particle Size analysis |

| |Bulk Density |

| |Tapped density |

| |Carr’s index |

| |Hauseners ratio |

| |Angle of repose |

| |IR Spectroscopy |

| |DSC |

| |X ray diffraction |

| | |

| | |

| |Evaluation of Tablets: |

| |Tablet dimensions |

| |Drug content uniformity |

| |Weight variation |

| |Tablet hardness |

| |Friability testing |

| |Disintegration time |

| |In vitro drug release studies |

| |Stability studies as per ICH guidelines. |

| | |

| |7.1 - Source of Data |

| |Internet. |

| |Review articles. |

| |Research publications. |

| |International and Indian journals. |

| |Textbooks and reference books |

| | |

| |7.2 - Method of collection of data |

| |The data will be collected from |

| |Prepared formulations. |

| |In vitro evaluation. |

| |Stability studies from various standard books. |

| |Journals. |

| |Other source like research literature data bases such as science direct |

| | |

| |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 clearance been obtained from your institution in case of 7.3? |

| | |

| |“NOT APPLICABLE” |

| | |

|8.0 |REFERENCES |

| | |

| |Spiras S, Bolton SM, Liquisolid systems and methods for preparing same, United States patent 5,1999,968,550. |

| |Bertocchi P, Antoniella E, Valvo L, Diclofenac sodium multisource prolonged release tablets- a comparative study on the dissolution |

| |profiles, J Pharm and biomedical analysis, 2005;37:679-685. |

| |Spireas S, Jarowski CI, Rohera BD, Powdered solution technology: principles and mechanism, Pharm. Res, 1992; 9 (10):1351–1358. |

| |Lobenberg R, Amidon, GL. Modern bioavailability, bioequivalence and biopharmaceutics classification system; new scientific approaches to |

| |international regulatory standards. Eur J Pharm Biopharm, 2000; 50: 3–12. |

| |5. Darwish AM., Dissolution enhancement of glibenclamide using liquisolid tablet |

| |technology, Acta Pharm, 2001; 51: 173-181. |

| |6. Patel VP, Patel NM, Dissolution enhancement of glipizide using liquisolid tablet |

| |technology, Ind Drugs, 2008; 45(4): 318-323. |

| |7. Fahmy RH, Kassem MA. Enhancement of famotidine dissolution rate through liquisolid |

| |tablet formulation: in vitro and in vivo evaluation, Eur J Pharm Biopharm, 2008; 69(3): |

| |993-1003. |

| |8. Spireas S, Sadu S, Grover R. In vitro release evaluation of hydrocortisone liquisolid |

| |tablets, J Pharm Sci, 1998; 87: 867-872. |

| |9. Spiras S, Wang T, Grover R, Effect of powder substrate on dissolution properties of |

| |methylclothiazide Liquisolid compacts, Drug Dev Ind Pharm, 1999; 25:163-168 |

| |10. Spireas S, Sadu S. Enhancement of prednisolone dissolution properties using liquisolid |

| |compacts. Int J Pharm, 1998; 166: 177-188. |

| |11. Javadzadeh Y, Shariati H, movahhed-danesh E, Effects of different grades of |

| |microcrystalline cellulose on flowability, compressibility and dissolution of liquisolid |

| |systems, Drug Dev Ind Pharm, 2008;1-9 . |

| |12. Javadzadeh Y, Navimipour B, Nokhodchi A. Liquisolid technique for dissolution rate |

| |enhancement of a high dose water insoluble drug (carbamazepine), Int J Pharm, |

| |2007:341:26-34. |

| |13. Javadzadeh Y, Siahi MR, Asnaashri S, Enhancement of dissolution rate of |

| |piroxicam using Liquisolid compacts, IL Farmaco, 2005; 60(4): 361-365. |

| |14. Rakshit P, Ridhish P, Moinuddin S, Formulation and evaluation of liquisolid |

| |compacts of piroxicam, Ind drugs, 2007,44(12):967-972. |

| |15. Tayel SA, Soliman I, Louis D. Improvement of dissolution properties of carbamazepine |

| |through application of the liquisolid tablet technique, Eur J Pharm Biopharm, 2008; |

| |69:342-347. |

| | |

| | |

| | |

| | |

| | |

| | |

| | |

| | |

| | |

| | | |

| | | |

|9. |SIGNATURE OF THE CANDIDATE | |

| | | |

| | | |

|10. |REMARKS OF THE GUIDE |Recommended |

| | | |

|11. |NAME AND DESIGNATION OF | |

| | | |

| |11.1 Guide |Mr. S.M.Patil (M. Pharm) |

| | |Professor |

| | |Department of Pharmaceutics |

| | | |

| |11.2 Signature | |

| | | |

| |11.3 Co-Guide ( If any) | |

| | | |

| |11.4 Signature | |

| | | |

| |11.5 Head of the Department |Prof. J.K.SABOJI |

| | |KLES’s College of Pharmacy |

| | |NIPANI-591237 |

| | | |

| |11.6 Signature | |

| | | |

|12. |12.1 Remarks of the Chairman |Forwarded to the University for approval |

| |Principal | |

| | | |

| |12.2 Signature | |

| | |Principal |

| | |KLES’s College of Pharmacy |

| | |Akkol road, Nipani, 591 237. |

................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download