FORMULATION AND EVALUATION OF ROFECOXIB LIQUISOLID TABLETS

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FORMULATION AND EVALUATION OF ROFECOXIB LIQUISOLID TABLETS: 

FORMULATION AND EVALUATION OF ROFECOXIB LIQUISOLID TABLETS Khalid M. El-Say, Ahmed M. Samy, Mohamed I. Fetouh. Dept. of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Nasr City, Cairo, Egypt. Presented by :- Malay Bhalodiya Mts.V.B.Manvar college of pharmacy,Dumiyani 1 guided by :- Dr. H. m. tank mr. sandip patel

CONTENTS: 

CONTENTS Abstract Key words Introduction Material and methods Results and discussion Conclusion References 2

ABSTRACT: 

ABSTRACT The aim of our study was to improve the availability of Rofecoxib a practically insoluble non-steroidal anti-inflammatory drug, as a model drug by using liquisolid technique. The effect of powder substrate composition on the flowability and compressibility of liquisolid compacts were evaluated. 3

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Specifically, several liquisolid formulations, containing 25-mg Rofecoxib, which containing different carrier to coating ratios in their powder substrates and a fixed liquid medication, were prepared. The dissolution profiles of Rofecoxib liquisolidtablets were determined according to USP method. The obtained dissolution profiles were compared to that of a commercial product. 4

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In the present study, the formulated liquisolid systems exhibited acceptable flowability and compressibility. In addition, liquisolid tablets displayed significant enhancement of the dissolution profiles compared to this of commercial one. Liquisolid tablets, Rofecoxib, Formulation and evaluation. KEY WORDS 5

INTRODUCTION: 

INTRODUCTION It is believed that better bioavailability of poorly soluble drugs could be achieved when drug is present in solution as in liquisolid formulations. The concept of liquisolid compacts as defined by Spireas et al, (1998) can be used to formulate liquid medication such as oily liquid drug and solutions or suspensions of water-insoluble solid drugs in non-volatile vehicles, into acceptably flowing and compressible powder. 6

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Using this new formulation technique, a liquid medication may be converted into a dry-looking, non-adherent, free flowing and readily compressible powder by a simple blinding with selected powder excipients referred to as carrier and coating materials. Various grades of cellulose, starch, lactose, etc, may be used as the carrier, whereas a very fine particle size silica powder may be used as the coating material. 7

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The technique of liquisolid preparations was used to formulate hydrochlorothiazide, as a model drug in tablet form. Rofecoxib drug profile :- Category: NSAID M.O.A.: inhibition of prostaglandin synthesis via inhibition of cox-2 Solubility: sparingly soluble in acetone, slightyl soluble in methanol, very slightyl soluble in ethanol, insoluble in water. 8

MATERIALS and methods: 

MATERIALS and methods Rofecoxib tablets 25mg (Egyptian International Pharmaceutical Industries Co.) Amorphous fumed silica, Cab-O-Sil® M-5P from Cabot Corporation (North America, USA), Methanol from Honil Limited (London), Methylene chloride, Propylene glycol, Glycerol, and Magnesium oxide(El-Nasr pharmaceutical chemicals Egypt) MATERIALS 9

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Microcrystalline cellulose, PEG 400, PEG 600, Tween 40,Tween 80, Brij 35% solution, and Span 80 (Sigma chemical Co. USA), Tween 20 (Aldrich chemical Co. Ltd. England), Ac-Di-Sol® “modified cellulose gum NF” (FMC corporation Philadelphia, Pennsylvania 19103, USA), Magnesium stearate (Prolabo France) Hydrochloric acid (Carloerba Milano, Italy). 10

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Shaking water bath (Julabo SW-20C, Germany), Ultraviolet spectrophotometer (Jenway 6305 uv/vis. UK), Single Punch tablet press (First Medicine machinery shanghai factory of Dongha Branch, Shanghai, China) Tablet Hardness tester (Pharmatest, Type PTB 301, Hainburg,Germany) Friability tester (Pharmatest, Type PTF1,Hainburg, Germany) Disintegration tester (Pharmatest, Type PTZ3, Hainburg, Germany) Dissolution apparatus, sixspindle dissolution tester (Pharma test Type PTWII, Germany). EQUIPMENTS 11

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Solubility studies:- The solubility of Rofecoxib was determined in different solvents including: PEG 600, PEG 400, Tween 80, Tween 40, Tween 20, Span 80, glycerin, Brij 35 solution, propylene glycol, and distilled water. EXPERIMENTAL Refecoxib + above solvent Sonicate (48 hrs) 12

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Cooled at 25 °C Filter with millipore filter Filter supernetant solution is diluted with methanol Analysed u.v.spectrophotomatrically at λ max 268 nm 13

EVALUATION OF FLOWABILITY AND COMPRESSIBILITY OF LIQUISOLID POWDERS: 

EVALUATION OF FLOWABILITY AND COMPRESSIBILITY OF LIQUISOLID POWDERS The flowability of the obtained mixtures, calculated by measuring angle of repose. Determination of bulk and tap densities of the obtained mixtures was used to calculate both the Hausner ratio and the Carr’s index. The obtained mixtures were compressed into tablets and the compressibility of these tablets was determined by measuring the hardness of each tablet. 14

Preparation of liquisolid tablets: 

Preparation of liquisolid tablets All liquid formulation containing different excipients ratio can be framed by using Box- Behnken design. Refecoxibe was dispersed in PEG 600 and mixure of excipients were added into mortar with continous stirring. Finally, Ac-Di-Sol® was mixed for a period 10 minutes and then adds magnesium stearate before compression. 15

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FORMULATION CHARACTERISTICS OF PREPARED ROFECOXIB LIQUISOLID COMPACTS 16

In-vitro release of Rofecoxib from liquisolid tablets: 

In-vitro release of Rofecoxib from liquisolid tablets Apparatus→USP XXV apparatus 2 14 . Temperature→ 37±0.5°C Rotation → 100 rpm Volume → 900 ml 0.1 N HCl P H → 1.2 Time intervals → 5,10,15,..45 min In vitro drug release → Determined by UV spectrophotometer.(268 nm) 17

RESULTS AND DISCUSSION: 

RESULTS AND DISCUSSION SOLUBILITY STUDIES OF DIFFERENT SOLVENTS Solvent Solubility (%w/w) PEG 600 1.0382 PEG 400 0.9669 Tween 80 0.8018 Tween 40 0.7602 Tween 20 0.6883 Span 80 0.6346 Glycerine 0.2405 Brij 35 solution 0.0567 Propylene glycol 0.0435 Distilled water 0.0023 18

EVALUATION OF FLOWABILITY AND COMPRESSIBILITY OF LIQUISOLID POWDERS: 

EVALUATION OF FLOWABILITY AND COMPRESSIBILITY OF LIQUISOLID POWDERS The powder has a good flowability ; when the Hausner ratio is lower than 1.2, while if the ratio is more than 1.2 this indicates that the flowability is bad. Compressibility is indirectly related to the relative flow rate, cohesiveness, and particle size of a powder. A compressible material will be less flowable , and powders with compressibility values greater than 20-21 % have been found to exhibit poor flow properties. 19

PHYSICAL PROPERTIES OF THE PREPARED ROFECOXIB LIQUISOLID POWDER: 

PHYSICAL PROPERTIES OF THE PREPARED ROFECOXIB LIQUISOLID POWDER 20

QUALITY CONTROL TESTS OF ROFECOXIB LIQUISOLID TABLETS: 

QUALITY CONTROL TESTS OF ROFECOXIB LIQUISOLID TABLETS 21

IN-VITRO RELEASE OF ROFECOXIB FROM LIQUISOLID TABLETS: 

IN-VITRO RELEASE OF ROFECOXIB FROM LIQUISOLID TABLETS The in-vitro release of Rofecoxib from the formulated liquisolid tablets were performed and the dissolution profiles of them from the prepared liquisolid tablets in 0.1N HCl pH 1.2 were graphically represented in figure. It was found that, all the prepared liquisolid tablets released more than 90% of their Rofecoxib content after 45 minutes. Figure 1: Dissolution profile of Rofecoxib liquisolid and commercial tablets 22

CONCLUSION: 

From the previous results, it was concluded that, addition of 10% Cab-O- Sil ® and 5% magnesium oxide improved both the flowability and the compressibility of the tested Rofecoxib powders. These two substances change the flowability from bad flow to satisfactory flow. Rofecoxib liquisolid tablets showed higher dissolution profiles than the three studied commercial tablet. CONCLUSION 23

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There is a relationship between the powder excipient ratio and the in-vitro release of Rofecoxib from liquisolid tablets having the same liquid load factor. The powder excipient ratio was directly proportional to the in vitro release of Rofecoxib from their formulations. Finally, Liquisolid technique can be used to improve the availability, and the in-vitro release of Rofecoxib as a model for a practically insoluble drug. 24

REFERENCES: 

REFERENCES Spireas, S., Bioavailability improvement of clofibrate using liquisolid compact technology, APHA Annual Meeting, 142, 161 (1995). Spireas, S., and Sadu , S., Enhancement of prednisolone dissolution properties using liquisolid compacts, Int. J. Pharm., 166, 177-188 (1998). Spireas, S.S., Theoretical and Practical Aspects of liquisolid compacts. Ph.D. Thesis, St. John’s University, New York, (1993). Khaled , A.K., Formulation and evaluation of hydrochlothiazide liquisolid tablets, Saudi Pharm. J.,6 (1), 39-46 (1998). 25

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Spireas, S., Sadu , S., and Grover, R., In vitro release evaluation of hydrocortisone liquisolid tablets, J. Pharm. Sci., 87, 867-872 (1998). Spireas, S., Wang, T., and Grover, R., Effect of powder substrate on the dissolution properties of methchlorothiazide liquisolid compacts, Drug Dev. Ind. Pharm., 25,163-168 (1999). Inas , A.D., and Amal , H.El ., Dissolution enhancement of glibenclamide using liquisolid tablet technology, Acta. Pharm., 51, 173 (2001). Egyptian Pharmacopoeia, (1984), Third Edition, vol. 1, p. 9. Fonner , D.E., Banker, G.S., and Swarbrick , J., J. Pharm. Sci., 55, 181 (1966). Carr, R.L., Chem. Eng., 72, 2, 163-168 (1965). 26

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Thank you 27