PREPARATION AND EVALUATION OF METRONIDAZOLE SUSTAINED RELEASE FLOATING TABLETS

Objective: The objective of the present study is the preparation of metronidazole (MZ) floating tablets that are designed to retain in the stomach for a long time for better eradication of Helicobacter Pylori (H. pylori), a main cause of peptic ulcer disease. Methods: Synthetic and natural polymers were studied for their floating potential in the presence of sodium bicarbonate, namely: hydroxypropyl methylcellulose (HPMC), carbopol 974P, sodium alginate{low and medium viscosity (LV & MV) grades}, locust gum and guar gum. Hardness, floating ability, release profiles and kinetics as well as DSC / FT-IR were studied. Results: Results of both DSC and FT-IR spectroscopy revealed that there was no interaction between the drug and any of the proposed polymers. Carbopol 974P based tablets showed an unacceptable floating lag time (2 h) and did not maintain good tablet integrity. All other formulas were able to float after few seconds and showed buoyancy for more than 24 h. Meanwhile, sustained profiles of MZ release were obtained. After 6 h the amount of MZ released were: 75.11 %, 61.26 %, 54.56 %, 54.25 % and 43.42 % from sodium alginate-LV, HPMC-K4M, guar gum, locust gum and sodium alginate-MV based tablets, respectively. Kinetically, among the 5 assessed models, the release pattern of MZ from the tablets fitted best to Zero order and Hixson & Crowell Cube-Root models. Conclusion: These stomach targeted dosage forms could maintain the minimum inhibitory concentration for sufficient time to allow for local eradication and thereby achieve better efficiency of therapy with improved patient compliance, reduced costs and minimized side effects caused by immediate release dosage forms

IN VITRO EVALUATION OF IBUPROFEN HOT-MELT EXTRUDED PELLETS EMPLOYING DIFFERENT DESIGNS OF THE FLOW THROUGH CELL

Objective: Hot-melt extrusion technique (HME) was used to prepare a sustained release (SR) multiparticulate oral dosage form (pellets) containing Ibuprofen (IBU). Prepared IBU-HME pellets were in vitro evaluated by flow-through cell dissolution tester (FTC, USP Apparatus #4) using different flow conditions and FTC designs. Methods: In this study, Sucroester®WE15 was used as the polymeric carrier to prepare two different IBU loadings (60 % and 30 % w/w). In order to optimize the FTC conditions, different cell sizes, pellets loading and hydrodynamic conditions of FTC on IBU release rate from pellets were proposed. Results: The results showed that the IBU release rate was increased in the larger cell than the small cell. In addition, laminar flow showed more reproducible results than turbulent flow. It was found that the large cell with laminar flow rate and homogeneous mixing of the pellets with glass beads was the optimum conditions for in vitro evaluation of these preparations. Conclusion: Improper methods of sample loading as well as cell size may result in confusing or erroneous data if not analyzed carefully. Therefore, it might be critical to choose a specific cell design of the FTC for in vitro evaluation of pellets to obtain reliable and discriminative results reflecting the major as well as minor formulation variables

IN-VITRO DISSOLUTION STUDY OF MELOXICAM IMMEDIATE RELEASE PRODUCTS USING FLOW THROUGH CELL (USP APPARATUS 4) UNDER DIFFERENT OPERATIONAL CONDITIONS

Objective: To evaluate and compare the in-vitro dissolution profiles of five generic immediate release (IR) products of Meloxicam (MX) available in Egyptian market with the innovator reference product (Mobic®, R) using different operational conditions of the flow through dissolution cell (FTC, USP Apparatus 4), in phosphate buffer (pH=7.5). Methods: The comparative in-vitro dissolution studies were performed under different FTC operational conditions such as cell size, tablet position within the cell, open and closed loops setup and type of flow (laminar and turbulent) on MX dissolution rate from different IR products. Results: The study showed that two generic products, out of five, gave similar dissolution profiles with R using a specified well controlled condition of FTC. A selected generic product (Mobitil, G1) was tested versus R under different operational conditions of the FTC such as cell size, type of flow, tablet position and open & closed loops setup. The dissolution profile of MX from R was highly affected by changing the tablet position, slightly affected by the open & closed loops setup and not affected by cell size and type of flow. On the other hand, the dissolution profile of MX from G1 was affected by all the previous operational conditions. Comparing ƒ2 values between G1 against R among the different operational conditions proposed, only one in-vitro dissolution test showed similar dissolution profile of G1 with respect to R. Conclusion: Three generic products of MX might not be interchangeable with the innovator product (Mobic®)

Disseminated angioinvasive basidiobolomycosis with a favourable outcome

Basidiobolomycosis, a rare fungal infection, is of worldwide distribution but areas commonly involved include the tropical areas of Africa, USA and South East Asia. 88% of the cases are reported among patients younger than 20 years. Many of the case reports in Saudi Arabia are from Tohama area where our patient lives. The diagnosis tends to be overlooked as the presentation may mimic colonic carcinoma in adults or inflammatory bowel diseases and tuberculosis in both children and adults. Angioinvasion seen in our patient is extremely rare suggesting the diagnosis of mucormycosis and resulting in a delay in choosing the most appropriate treatment. We report this case to remind physicians and surgeons to consider this diagnosis in patients from endemic area presenting with such conditions. Keywords: Zygomycetes, Basidiobolomycosis, Mucormycosis, Eosinophilia, Angioinvasio

Genetic polymorphisms of fecundity genes in Watish Sudanese desert sheep

Background and Aim: The Watish sheep is a strain of desert sheep of smaller size compared to other desert sheep ecotypes, and there is anecdotal evidence that it is endowed with high litter size. The present study was designed for screening for polymorphisms in the known fecundity genes (bone morphogenetic protein receptor type 1B A<G in exon 6, bone morphogenetic protein 15 (BMP15) (FecXB, FecXG, FecXH, and FecXI) in exon2, growth differentiation factor 9 (GDF9) – G1 in exon1 and G8 in exon2 and PRLG<A in intron2) and their association with litter size in Watish. Materials and Methods: The study involved 156 Watish ewes of 2-6 years of age, along with data on litter size in the first, second, and third parity from Sinnar state and contiguous Blue Nile State. Genomic DNA was isolated and genotyped using polymerase chain reaction-restriction fragment length polymorphism. Allele and genotype frequencies were calculated by direct counting. Chi-square test for goodness of fit was performed for agreement with Hardy-Weinberg expectations and association testing. Results: The results demonstrated that all individuals were non-carriers for the target mutations of FecB, BMP15 (FecXB, FecXH, and FecXI), and GDF9-G8. With regard to the GDF9-G1 gene, the genotypic frequencies were 0.07% (G+) and 0.93% (++), in FecXG gene they were 0.993% (++) and 0.006% (B+), in PRL gene 0.516(++), 0.347(B+), and 0.137(BB). The Chi-square test showed a non-significant association between ewe's type of birth and the detected mutations genotypes. Conclusion: These results preliminarily indicated that GDF9-G1, BMP15 (FecXG), and PRL genes might have had some contribution for improving litter size in Watish Sudanese sheep. However, further studies using larger samples are needed to detect the effects of those mutations on Watish sheep litter size