Design and evaluation of gastroretentive mucoadhesive cephalexin tablets.

The aim of this investigation was to develop gastroretentive mucoadhesive tablets of cephalexin, which will retain in the stomach for 10 h. Cephalexin, a first-generation cephalosporin, becomes ionized in intestinal pH because pKa is 4.5 and thus reducing its bioavailability. The various batches were prepared by wet granulation method using variety of mucoadhesive polymers such as hydroxyl propyl methyl cellulose K4M, hydroxyl propyl cellulose, chitosan, carbopol 934P and sodium carboxymethylcellulose and subjected to various evaluation parameters such as mucoadhesive strength, in vitro drug release profile, swelling characteristics and physical properties. It was evident from the study that the formulation containing HPMC K4M and carbopol 934P in combination exhibited maximum mucoadhesive strength of 144.42 gms, in vitro residence time was 8.73 h and in vitro drug release was found to be 75.03% in 10 h with non-Fickian diffusion mechanism. So, the optimized formulation F(2) was further subjected to in vivo retention time in rabbit by X-ray technique, SEM and Accelerated stability studies. Regarding all the properties evaluated, the formulation containing HPMC K4M and carbopol 934P in combination was found to be the best to achieve the aim of this study.

Design and study of rifampicin oral controlled release formulations.

Oral controlled release formulations of rifampicin have been developed by using hydroxypropyl methylcellulose polymer at different ratios. From in vitro release data, we found that the release was extended with an increase of polymer proportion from 20% to 40%. However, increase in polymer beyond 40% resulted in no significant change in the release rate. There was a distinct difference in the release rate and release character due to variation in the compression force. The release kinetics were analyzed using Ritger and Peppas exponential equation. Stability studies at ambient storage conditions for 1 year showed that formulations were stable.

Potential transition state phosphoramidate inhibitors of beta-tubulin as antifilarial agents.

Transition state phosphoramidate inhibitors of beta-tubulin were designed as potential antifilarial agents. The reaction of 2-aminobenzimidazole with diisopropyl phosphite and carbon tetrachloride at a low temperature gave the unexpected 1-diisopropoxyphosphoryl-2-aminobenzimidazole, which on heating gave the novel benzimidazole derivative, 2-(diisopropoxyphosphoryl)aminobenzimidazole. Both products were fully characterized and the synthetic procedure to both compounds was optimized. The procedure was used to prepare the related 5-benzoyl-2-(diisopropoxyphosphoryl)aminobenzimidazole and 5-benzoyl-2-(diethoxyphosphoryl)aminobenzimidazole (1d). In a preliminary trial against Brugia pahangi compound 1d was found to have no antifilarial activity. This lack of activity may be attributed to its extreme insolubility and thus low bioavailability. The synthesis of analogous, more soluble, phosphorothioate-substituted benzimidazoles using the same methods may yield compounds with greater antifilarial activity.

Antifertility and hormonal properties of flavones of Striga orobanchioides.

The two flavones, apigenin and luteolin, isolated from Striga orobanchioides, were investigated for endocrine and contraceptive properties. Graded doses of these compounds (5-25 mg/kg body weight/day) when administered from day 1 to day 4 of pregnancy showed dose-dependent and significant anti-implantation activity. The mean effective Dose 100% (MED(100)) for both compounds was found to be 25 mg/kg body weight. Oral administration of these compounds caused a significant increase in uterine weight in immature ovariectomised rats. It also caused a significant increase in uterine diameter, thickness of the endometrium and its epithelial cell height when compared with those of control rats. The uterotrophic potency was less than that of ethinyl estradiol. Simultaneous administration of these compounds with ethinyl estradiol caused a significant increase in uterine weight, uterine diameter, thickness of the endometrium and height of endometrial epithelium. The extent of these changes was also less than that in only ethinyl estradiol-treated rats. Hence the compounds exhibited estrogenic properties at their contraceptive dose level when given alone. However, along with ethinyl estradiol, they exhibited slight anti-estrogenic activity.

Post-coital antifertility activity of Acalypha indica L.

Four successive solvent extracts of the whole plant Acalypha indica L. (Euphorbiaceae) were tested for post-coital antifertility activity in female albino rats. Of these, the petroleum ether and ethanol extracts were found to be most effective in causing significant anti-implantation activity. The antifertility activity was reversible on withdrawal of the treatment of the extracts. Both the extracts at 600 mg/kg body weight showed estrogenic activity. Histological studies of the uterus were carried out to confirm this estrogenic activity.

Antiandrogenic effect of Striga orobanchioides.

The ethanolic extract of the whole plant of Striga orobanchioides given for 7 days to immature male rats at a dose level of 200 mg/kg body weight caused a significant decrease in the weight of the testes, epididymis, seminal vesicles and the ventral prostate. It also produced degenerative changes of Leydig cells, their nucleus, the seminiferous tubules and a significant decrease in the number of spermatocytes and spermatids. The seminiferous tubules of the treated rats are shrunken and compactly arranged. The antiandrogenic or antispermatogenic effect of the extract is discussed.

Antifertility activity of Striga orobanchioides.

Four successive solvent extracts of the whole plant Striga orobanchioides have been screened for antifertility activity in albino rats. Of these the ethanolic extract was found to be most effective in causing significant anti-implantation activity. The antifertility activity was reversible on withdrawal of treatment with the extract. The ethanolic extract at 200 mg/kg showed estrogenic activity. Histological studies of the uterus were carried out to confirm this estrogenic activity.

Possible antifertility agents belonging to substituted indoles.

Of the 21 compounds evaluated for antiimplantation and abortifacient activities, compounds (A1, A2, A4 and B1) and compounds (C1, C2, D1 and D3) were found to exhibit 40% and 30% antiimplantation activity, respectively, in female rats when given orally on days 1-5 postcoitum. The remaining 13 compounds were found to be inactive. All of the 21 compounds were also tested for the abortifacient activity, but all were found to be inactive.

Antifertility efficacy of the plant Striga lutea (Scrophulariacae) on rats.

Acacetin and luteolin, the flavones isolated from the whole plant S. lutea, have been investigated for endocrine and contraceptive properties in the pre-implantation stage of pregnancy. Graded doses of these compounds, in gum acacia suspension, by oral administration from day 1 to day 4 of pregnancy showed dose-dependent anti-implantation activity (5-25 mg/kg body weight/day). MED100 was found to be 25 mg/kg body weight in the day 1-4 regimen in rats for both the compounds. In another study, a single oral dose of these compounds (10 mg/kg body weight) on day 1, 2 or 3 of pregnancy prevented 100% implantation. The compounds exhibited estrogenic property at their contraceptive dose level but failed to show antiestrogenic activity.

Antifertility activity of striga lutea--Part I.

The petroleum ether and chloroform extracts of the whole plant striga lutea have been found to possess significant antifertility activity in mice. Both these extract exhibited complete and partial resorption of implants at a dose of 100 mg/kg and 50 mg/kg body weight, respectively. Histological studies of the uterus and ovary were carried out to confirm the antifertility activity of these extracts.