Description:DETAILED DISCRIPTION OF INVENTION
Present invention relates to develop and optimize sustained release oral product of Famotidine using sodium alginate beads as hydrophilic microbeads carrier.
EXAMPLES
Preparation of Beads
In the present study an attempt was made to formulate sustained release microbeads of Famotidine from sodium alginate with different release modifiers such as HPMC K4M, Carbopol 71G and Pectin so as to enhance bioavailability and to reduce dosing frequency of the selected drug.
The goal of any drug delivery system is to provide a therapeutic amount of drug to the proper site in the body and also to achieve and maintain the desired drug concentration. This could be achieved through Multiparticulate dosage like beads which is divided into many individual units, so-called subunits, each exhibiting some desired characteristics.
An attempt is made to develop microbeads by Ionotropic Gelation and cross linking Technique with a view to improve bioavailability, and also to reduce dose frequency and thereby to achieve an oral controlled release of the drug.
From FT IR study, it was concluded that there was no interaction between polymers and drug. All the polymers used were compatible with the drug.
Placebo beads were prepared by Ionotropic gelation and cross linking
method by Using Sodium alginate and various types of different concentration of hydrophilic polymers such as HPMC K4m, Carbopol, and Pectin as release modifiers, Calcium chloride as counter ion and glutraldehydeas cross-linking agent. Sixteen batches of placebo micro beads were prepared with different concentration of polymers and they were coded.
Drug In Vitro Release Study
All the prepared placebo beads were subjected to evaluation parameters like percentage yield, Particle size analysis, drying rate study and Swelling behavior.
Percentage yield of beads were found in the range of 73-95%
Particle size of gel beads were found in the range of 1103±0.8 to1399±1.2micrometer.
Swelling index of gel beads were in range of 940±0.9 to 1874 ±3.4 %
Based on the highest percentage yield, and least beads size and high swelling index, few batches were selected for drug loading. Batches with 2% of sodium alginate and 1% of release modifier like HPMC K4M, Carbopol and Pectin.
Drug loaded beads were prepared by same method and same polymer but only the difference was the concentration of drug FAMOTIDINE. Four different concentration of drug Famotidine such as 10mg, 20mg, 30mg & 40mg were added to the optimized batch of polymers.
All the drug loaded beads were subjected to evaluation parameters like percentage drug entrapment, loose surface crystal study and in vitro release study. Based on the highest Percentage entrapment, more loose surface crystals and better sustained effect, the batches, like FH1, FC2 & FP1 were found to be better than other batches.
Selected batch such as FH1, FC2 & FP1 were subjected to in vitro release kinetic study, stability study and was found to exhibit zero order kinetics with release mechanism of super case II-transport and they were found to be stable when stored at room temperature for 45 days.
Scanning electron microscopic study of selected batch FH1 was found out and it revealed that the microbeads were almost spherical in shape with rough outer surface. , Claims:We claim,
Claim 1: An oral pharmaceutical formulation containing famotidine or a famotidine-related compound, or a pharmaceutically acceptable Salt thereof, as active ingredient, wherein said formulation exhibits controlled in vitro release of the active ingredient in phosphate buffer at pH 6.8 of not less than about 80% after 18 hours, and after oral administration to a patient is capable of maintaining a Substantially constant serum level of the active moiety or moieties for 24 hours.
Claim 2: The formulation according to claim 1, wherein the fraction of famotidine, famotidine-related compound or Salt thereof that is released in vitro is not less than about 80% after 15 hours.
Claim 3: The formulation according to claim 1, wherein the in Vitro release is measured by a drug release test which utilizes the United States Pharmacopoea (USP) Apparatus 1 (rotating basket) at 100 rpm with 900 ml of deaerated phosphate buffer at pH 6.8 and 37 C., where the phosphate buffer solution is prepared as described on pages 2049-2050 of USP 23, and nominally contains 0.05 M phosphate.
Claim4: A method of treating heartburn, which comprises administering a therapeutically effective amount of a pharmaceutical formulation according to claim 1.