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Department of Pharmacetical Chemistry, College of Pharmacy, Salman Bin Abdulaziz University, Al-Kharj, Saudi Arabia  Gastric region is one of the main.

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Presentation on theme: "Department of Pharmacetical Chemistry, College of Pharmacy, Salman Bin Abdulaziz University, Al-Kharj, Saudi Arabia  Gastric region is one of the main."— Presentation transcript:

1 Department of Pharmacetical Chemistry, College of Pharmacy, Salman Bin Abdulaziz University, Al-Kharj, Saudi Arabia  Gastric region is one of the main regions of many infections such as H. pyloric and diarrhoea in human body. Helicobacter pyloric infection is the one of the main cause of the gastritis, whereas diarrhoea and cholera are one of main diseases that claim uncountable lives annually in underdeveloped and developing countries.  Ofloxacin is used in the treatment of cholera, dysentery and diarrhea.  Hydrodynamically Balanced System (HBS) capsules have been designed as single unit gastroretentive drug delivery system (GRDDS), whereas, hollow microspheres have been prepared as multiple unit system for the GRDDS to eradicate bacterial infection in gastric region.  Multiple units have an advantage over single unit as it eradicates the ‘All or none’ effect of single unit dosage form and reduces chances of dose dumping. Multiple units dosage form have added advantage of better dose uniformity.  Polymers which enable the system to achieve a density of less than 1 in dissolution media were selected. Different grades of HPMC and PEO were selected and physically blended with drug and filled in a hard gelatin capsule (size 0). No other exceipients were added. Cellulose acetate phthalate (CAP), liquid paraffin and ethyl cellulose were used as release modifiers in order to achieve release from the delivery system for a period of 12 hours. Liquid paraffin and CAP were physically mixed with the mixture of polymers and drug, whereas, ethyl cellulose in ethanol was used to coat the drug particles prior to physical mixing with the polymer for release modification of the formulation.  Microspheres using various grades of polyethylene oxide and Eudragit were prepared using solvent diffusion technique and ofloxacin was loaded in the formulation.  Floatation studies of HBS capsules was carried out in USP apparatus II. The formulation was placed in 900 ml of citrate phosphate buffer pH 3.0 The time taken by the dosage form to sink in the dissolution media was recorded as floating time of the formulation. Whereas, for multiple unit system, microspheres were spread over the surface of the dispersing medium and agitated at speed of 50 rpm. The fraction of microspheres which remained floating on surface after 12 hours were separated and used to calculate buoyancy of microspheres.  In vitro dissolution studies were carried out in USP dissolution apparatus II using 900 ml of the dissolution medium constituting of buffer pH 3.0 and 0.5% sodium lauryl sulphate (SLS) at 37ºC (  0.5ºC). Speed was adjusted to 100 rpm. The samples were withdrawn periodically over a period of 12 hours and analysed using Shimadzu UV spectrophotometer UV-1601.  The optimized formulation showed an entrapment of 57.67%. The entrapment efficiency was justified by the fact that polyethylene oxide facilitates diffusion of a part of entrapped drug to the surrounding medium during preparation of floating microspheres. Eudragit L being a film forming polymer has lesser permeation characteristics and is simultaneously able to retain more of the entrapped drug.  It was found that most of the microspheres (56.95%) were still floatable after 12 hours because of their low densities and also owing to the internal voids. The hollow structure of the microspheres was estimated by measuring particle density (  ) by liquid displacement method. Calculation of porosity and the diameter to shell thickness ratio (D/T) was done. A porosity of 61.14% and D/T ratio of 12.9% confirmed the hollow nature of the microspheres. Ofloxacin followed Higuchi model for release from formulation. Fig. 2: In vitro release profile for optimized microspheres It can be concluded that HBS capsules made from PEO 60K and ethyl cellulose coated ofloxacin was found out to be effective as single unit gastroretentive drug delivery system. A stable formulation has been developed that can target ofloxacin effectively to the gastric region. The microspheres made of polyethylene oxide and Eudragit L were found to be effective as multiple unit gastroretentive dosage form targeting ofloxacin effectively to the gastric region. The optimized single and multiple unit system showed nearly same in vitro dissolution pattern, but different drug release mechanism in release model. The HBS capsules released drug by Higuchi model predicting matrix type of release, where as, microspheres showed Fickian release predicting diffusion release from the outer suface of microspheres.  Ali, J. et al., Methods & Find. in Exp. Clin. Pharm. 28, (2006) 1-7  Kawashima, Y. et al., J. Control. Release, 16, (1991), 279-290  Srividya, B. et al., Ind. Drugs, 40 (1), (2002) 41-44. Pharmaceutical Sciences World Congress, 22 nd – 25 th April 2007, Amsterdam, The Netherlands The dissolution studies of HBS capsules revealed that almost 96% drug was released within 9 hours, hence it was decided to use release modifiers to extend the release of drug up to 12 hours. The release could be sustained for over a period of 12 hours and the best results were obtained with the formulation containing 2.5% of ethyl cellulose and hence it was chosen as optimized formulation with in vitro release of 96.02%. (Fig.1) The in vitro release data from optimized formulation. was subjected for establishing mechanism of drug release. A good R 2 value was obtained for Higuchi model. Thus it can be concluded that ofloxacin follows Higuchi model for release. Microspheres prepared from combination of Eudragit L-100 and PEO N80 in solvent system of dichloromethane and ethanol at 25 o C was found out to be the best and exhibited the maximum drug release of 95.83% in 12 hours. Therefore this formulation was taken as optimized formulation. This formulation contained 200 mg of Polyethylene oxide N80, 400 mg of Eudragit L-100 and 200 mg of ofloxacin. Fig. 1: In vitro release profile for optimized HBS capsule The authors are grateful to All India Council of Technical Education, New Delhi for `Career award for young teachers` as financial support for this project and PSWC-FIP for providing travel grant to attend this conference. SYNTHESIS,SPECTRAL CHARACTERIZATION OF SUBSTITUTED QUNAZOLINE DERIVATIVES FOR ANTMICROBIAL AGENTS I N T R O D U C T I O N E X P E R I M E N T A L M E T H O D S R E S U L T S & D I S C U S S I O N R E F E R E N C E S C O N C L U S I O N S A C K N O W L E D G E M E N T S


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