balu review 1

Formulation of hard gelatin capsules of valsartan :

Formulation of hard gelatin capsules of valsartan by under the guidance of balakrishna.t Prof. M. Eswar Gupta, II M.pharmacy Dept of pharmaceutics, Chalapathi Institute of Pharmaceutical Sciences

DRUG PROFILE:

DRUG PROFILE Category : Antihypertensive. Dose : 80 – 160mg Color : white Molecular weight : 435.5188 Solubility : freely soluble in methanol and practically insoluble in water. Water solubility : 2.34e-02 g/l. Ref : drugbank .com

AIM:

AIM TO formulate fast dissolving hard gelatin capsules of Valsartan .

INTRODUCTION:

INTRODUCTION Valsartan is an antihypertensive drug belonging to the class II according to the BCS classification. It has low solubility and high permeability. Its bioavailability is dissolution rate limited.

Literature review:

Literature review Literature review indicates that attempts were made to enhance dissolution rate of valsartan by complexation with cyclodextrins and by preparing solid dispersions using skimmed milk / pvp / hpmc etc. No one has tried formulating capsules, and there are no capsules of valsartan on indian market.

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Literature review indicated that a number of methods of analytial estimation of Valsartan. We used I.P method as it was simpler. Ref : A.Sibel , S.E.Ozakan , N.Gorger , S.Altinay and S.Zuhre , Simultaneous determination of valsartan and Hydrochlorthiazide in tablets by first-derivative UV spectrophotometry and LC , J. Pharm. Biomed Anal, 25(5) ,1009-1013, 2001. N.Daneshtalab , R.Z.Lewanczuk , and J.Fakherddin , High-Performance liquid Chromatographic analysis of angiotensin II receptor antagonist valsartan using a liquid extraction method , J. Chromatogr . B. Analyt . Technol. Biomed and Life sci , 766(2) , 345-349, 2002. P.S.Selvan , K.V.Gowda , U.Mandal , W.D.Solomon , and T.K.Pal , Simultaneous determination of fixed dose combination of nebivolol and valsartan in human plasma by liquid chromatographic-tandem mass spectrometry and its application to pharmacokinetic study , Journal of Chromatography, 858(1-2) , 143-150, 2007. Indian Pharmacopoeia , The Indian Pharmacopoeial Commission, Ghaziabad, 6(3) , 2286, 2010.

Pharmacokinetic profile of valsartan :

Pharmacokinetic profile of valsartan Absorption : Absolute bioavailability = 23% with highvariability Protein binding : 94 - 97% bound to serum proteins,primarily albumin Half life : The initial phase t 1/2 α is < 1 hour while the terminal phase t 1/2 β is 5-9hours Volume of : 17 L distribution Clearance : 2 L/h [IV administration] 4.5 L/h [heart Failure patients receiving oral administration 40 to 160 mg twice a day] Ref : drug bank .com

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As valsartan is a BCS class II drug, it has been decided to develop fast release formulations. In general drug will dissolve faster from hard gelatin capsules than tablets.

Work done:

Work done Construction of calibration curve of valsartan in pH 6.8 phosphate buffer. Dissolution of capsules containing only valsartan without any additives.

Calibration of valsartan by U.V :

Calibration of valsartan by U.V Preparation of phosphate buffer: 6.84 g of potassium dihydrogen ortho phosphate and 0.89 g of sodium hydroxide were dissolved in distilled water and volume was made up to 1000 ml with distilled water. Standardization : The calibration curve of valsartan was done according to IP method. The valsartan obeys Beers law in the range of 5 to 30 µg / ml at 250 nm. Ref : Indian Pharmacopoeia , The Indian Pharmacopoeial Commission, Ghaziabad, 1 , 477, 2007.

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Table 4.1: Absorbance of Valsartan Standard Solutions S.No Concentration µg/ml Absorbance at 250 nm Average S.D % RSD Trial 1 Trial II Trial III 1 5 0.216 0.208 0.212 0.212 0.004 1.886 2 10 0.374 0.361 0.391 0.375 0.015 4.008 3 15 0.488 0.488 0.49 0.489 0.001 0.236 4 20 0.63 0.651 0.658 0.646 0.015 2.254 5 25 0.802 0.775 0.835 0.804 0.03 3.737 6 30 0.998 0.947 0.949 0.965 0.028 2.994 S.D is standard deviation, % RSD is % Relative standard deviation

Dissolution studies of valsartan:

Dissolution studies of valsartan The dissolution of pure drug capsule was done according to IP method in pH 6.8 phosphate buffer. Type : paddle Dissolution medium : pH 6.8 phosphate buffer (900 ml). Temperature : 37.5 ± 0.5 0 C. Speed : 50 rpm Sinker : copper wire Wavelength : 250 nm. Ref : 1. Indian Pharmacopoeia , Indian Pharmacopoeial Commission, Ghaziabad, 3 , 2286, 2010. 2. Jennifer Dressman , Johannes Kramer, Pharmaceutical Dissolution Testing , Taylor and Francis, Newyork , 49, 2007.

Dissolution Profile of Pure Drug of Valsartan:

Dissolution Profile of Pure Drug of Valsartan S.No Time in minutes % Drug dissolved Average % Un dissolved log %Undissolved S.D T 1 T 2 T 3 1 0 0 0 0 0 100 2 0 2 10 13.5 11.1 20.9 15.2 84.7 1.927 5.0 3 20 16.1 16.7 20.1 17.6 82.3 1.915 2.1 4 30 34.8 31.9 29.8 32.2 67.7 1.830 2.4 5 45 57.4 51.8 57.3 55.5 44.4 1.646 3.2 6 60 80.6 68.8 76.9 75.4 24.5 1.380 6.0 S.D is Standard Deviation

Dissolution Plots of Pure Drug of Valsartan:

Dissolution Plots of Pure Drug of Valsartan

Dissolution Rate Testing Parameters of Formulation A:

Dissolution Rate Testing Parameters of Formulation A Parameter Value K 0 1.248 % / minute R 2 0.981 K 1 0.0112 % / minute R 2 0.927 T 50 (Time for 50 % of VST to dissolve) 40.0 minutes T 90 (Time for 90 % of VST to dissolve) 72.1 minutes DP 10 (% of VST dissolved in 10 minutes) 12.4 % DP 30 (% of VST dissolved in 30 minutes) 37.2 % DP 45 (% of VST dissolved in 45 minutes) 55.8 % DP 60 (% of VST dissolved in 60 minutes) 74.4 % DE 10 (Dissolution efficiency at 10 minutes) 51.7 % DE 30 (Dissolution efficiency at 30 minutes) 49.5 % DE 45 (Dissolution efficiency at 45 minutes) 45.0 % DE 60 (Dissolution efficiency at 45 minutes) 46.0 %

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Thank u