S.B. Bhise’s research while affiliated with Sinhgad Institute of Pharmaceutical Sciences and other places

Gliclazide (GLI), a poorly water-soluble antidiabetic, was transformed into a glassy state by melt quench technique in order to improve its physicochemical properties. Chemical stability of GLI during formation of glass was assessed by monitoring thin-layer chromatography, and an existence of amorphous form was confirmed by differential scanning calorimetry and X-ray powder diffractometry. The glass transition occurred at 67.5°C. The amorphous material thus generated was examined for its in vitro dissolution performance in phosphate buffer (pH 6.8). Surprisingly, amorphous GLI did not perform well and was unable to improve the dissolution characteristics compared to pure drug over entire period of dissolution studies. These unexpected results might be due to the formation of a cohesive supercooled liquid state and structural relaxation of amorphous form toward the supercooled liquid region which indicated functional inability of amorphous GLI from stability point of view. Hence, stabilization of amorphous GLI was attempted by elevation of T g via formation of solid dispersion systems involving comprehensive antiplasticizing as well as surface adsorption mechanisms. The binary and ternary amorphous dispersions prepared with polyvinylpyrrolidone K30 (as antiplasticizer for elevation of T g) and Aerosil 200® and/or Sylysia® 350 (as adsorbent) in the ratio of 1:1:1 (w/w) using kneading and spray-drying techniques demonstrated significant enhancement in rate and extent of dissolution of drug initially. During accelerated stability studies, ternary systems showed no significant reduction in drug dissolution performance over a period of 3 months indicating excellent stabilization of amorphous GLI.

Alocasia indica Schott (Araceae) is used in several regions of India, especially in rural communities, by traditional medicine practitioners to treat diarrhea. However, no scientific data are available to justify the traditional potentials of the plant species in gastrointestinal disorders. To evaluate the antidiarrheal and in vitro antiprotozoal activities of extracts of leaves of Alocasia indica using various pharmacological models. In vitro antidiarrheal activity of aqueous and ethanol extracts of Alocasia indica was evaluated against Escherichia coli, Salmonella typhimurium, Shigella flexneri and Staphylococcus aureus by agar well diffusion method. In vivo antidiarrheal activity of the extracts was studied against recinolic acid-induced diarrhea and magnesium sulfate-induced diarrhea. The effect of the extracts on normal intestinal transit, recinolic acid-induced intestinal transit, recinolic acid-induced intestinal fluid accumulation (enteropooling) and gastric emptying was assessed. In vitro antiprotozoal activity of aqueous and ethanol extracts of Alocasia indica was studied against Entamoeba histolytica and Giardia intestinalis. The aqueous and ethanol extracts exhibited significant in vitro antidiarrheal activity compared to the standard drug ciprofloxacine (10 µg/mL). The plant extracts showed significant (P <0.05) and dose-dependent antidiarrheal activity comparable to that of the reference drug, loperamide (10 mg/kg). The plant extracts exhibited significant in vitro antiprotozoal activity against both protozoa compared to the standard amebicidal and giardicidal drugs, metronidazole and emetine. The results showed that the extracts of Alocasia indica have significant antidiarrheal and in vitro antiprotozoal activities which support its use in traditional herbal medicine practice.

The front line antitubercular drugs rifampicin (RMP) and isoniazid (INH), when co-administered, face the problem of reduced bioavailability of RMP. Stabilization of RMP in the presence of INH under acidic environment may improve the bioavailability of RMP. In vitro degradation studies showed around 15-25% degradation of RMP under the aforesaid conditions if the ratio of RMP: INH is above 1:0.5.This degradation is reduced to less than 10% when the ratio of RMP: INH is below 1:0.25. Based on these findings, an innovative drug delivery system was designed with the immediate release of RMP and tailored prolonged release of INH. The bilayer tablets prepared with this concept were subjected to relative bioavailability studies in healthy human volunteers in an open label, balanced, randomized, single-dose, cross-over study under fasted state. A validated LC-MS/MS bioanalytical method was employed for estimation of RMP and INH in plasma. Bioavailability studies revealed that C(max) and AUC for RMP increased by 18 and 20%, respectively, confirming the above innovative concept. Even in the case of INH, AUC increased significantly by around 30% and thus time above minimum inhibitory concentration (MIC) would also increase, which may result in further improved clinical outcome.

In an attempt to improve the dissolution rate of poorly aqueous soluble diacerein (DCN), solid dispersions (SDs) were prepared with a surfactant Pluronic® F 127 (PXMR) at drug to polymer ratios of 1:0.5, 1:1.5, and 1:2.5 (w/w) by an ordinary melting technique. The interaction of DCN with PXMR in all solid binary systems was evaluated by thin layer chromatography (TLC), Fourier transform infrared spectrometry (FTIR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM) studies. TLC indicated an absence of chemical interaction of DCN with PXMR whereas FTIR studies demonstrated an existence of strong hydrogen bonding between them. A uniform molecular dispersion of DCN was observed in DSC thermograms, and this finding was further supported by loss of the crystalline and irregular shape of DCN detected in SEM photomicrographs. Dissolution studies were promptly conducted to examine the release rate performance of DCN from all binary systems. The drug dissolution properties of binary systems improved significantly in comparison to crystalline DCN. The rate and extent of DCN release were observed to be strongly dependent on the proportion of PXMR present within the formulations.

Several polyphenols have been tested in Nymphaea stellata, Willd. The flavonoid content is important because of the pharmacological properties of these compounds, whereas quercetin has been proved to be an antioxidant, antiinflammatory and hepatoprotective compound. A reversed-phase HPLC method has been developed and applied to determine quercetin content in hydroalcoholic extract of dried flowers of Nymphaea stellata in a single analysis. The gallic acid was analyzed with a HiQ Sil C-18 column by isocratic elution using 0.01 % (v/v) orthophosphoric acid:acetonitrile (95:5 v/v) as the mobile phase. The flow rate was 1.2 mL min-1 and detection was set at 265 nm. The recovery of the method was in the range of 98.50-99.40 % and all the compounds showed good linearity (r = 0.98332) in a relatively wide concentration range.

Rifabutin is a rifamycin antibiotic with potential and established application against mycobacterium avium complex (MAC). Use of rifabutin has also been advocated in place of rifampicin in rifampicin-resistant cases. Isoniazid (INH) is a time-tested and well established drug for treatment of tuberculosis. To determine the stability of rifabutin and INH in a combination dosage form, a rapid, selective, and stability-indicating high-performance thin-layer chromatographic (HPTLC) method has been established and validated for simultaneous analysis of rifabutin and INH. Aluminum foil HPTLC plates coated with silica gel 60F 254 were used with dichloromethane-acetone- methanol 20:7:2 (v/v) as mobile phase. This system gave compact bands for both rifabutin (R F 0.84 ± 0.01) and INH (R F value of 0.48 ± 0.01). Spectrodensitometric scanning-integration was performed at 504 nm and 262 nm for rifabutin and INH, respectively. Polynomial regression data for the calibration plots showed response was a linear function of amount of drug in the concentration ranges 10 to 70 μg for rifabutin (correlation coefficient, r 2 = 0.9991) and 5 to 35 μg for INH (r 2 = 0.9989). The method was validated for specificity, linearity, precision, accuracy, and robustness. The limits of detection (LOD) were 180 ng and 90 ng and the limits of quantification were 540 ng and 270 ng for rifabutin and INH, respectively. The method was able to separate the degradation products of rifabutin from the active drugs, and so can be regarded as stability-indicating. Statistical analysis proves the method is reproducible and selective for simultaneous analysis of rifabutin and INH.

The present review supports novelty and applicability of Stevia rebaudiana through history, traditional uses, phytochemistry, phytochemical screening, pharmacological actions, human safety trials and clinical evaluation. Stevia rebaudiana contains over 100 phytochemicals including well characterized stevioside and rebaudioside A. It is well known for its application in treatment of many diseases like diabetes, hypertension, weight loss, antimicrobial in various traditional system of medicine. In recent times, the extract has been subjected to chemical, biochemical, pharmacological, clinical and toxicological investigation and many new therapeutic applications have emerged out. In addition it also contains nutrients therefore it acts as a best nutraceutical. There has been a great interest in exploration and use of this natural sweetener in the field of pharmacy. Thus, from the overall study it reveals that Stevia rebaudiana may be a versatile natural sweetener and nutraceutical if used in sweet formulations.

Carbamazepine (CBZ), a major antiepileptic drug, has poor solubility but good permeability. CBZ is classified as class II drug in Biopharmaceutical Classification System (BCS). Low aqueous solubility and high dose of CBZ offers poor and erratic solubility and dissolution. The present investigation is aimed to explore the effect of various doses such as 40 mg, 100 mg and 200 mg on dissolution of CBZ different gastrointestinal fluids. Low dose of 40 mg provided complete drug release with simulated gastric fluids. However, in intestinal fluids the drug dissolution rate was much slower than gastric fluids. The research observations revealed that there is a strong correlation between pH of dissolution media and drug release. The probable reasons for enhanced dissolution of CBZ (40 mg as a low dose) was due to sink conditions of drug in dissolution media that prevent the crystallization of CBZ dihydrate and showed 100% drug release in fasted state simulated gastric fluid (FaSSGF) within 50 min. The dissolution profile of 100 mg dose of CBZ was studied in FaSSGF and simulated gastric fluids (SGF), and was found be 88.8% and 83.27%, respectively, this is comparably higher than intestinal fluids. In one of the media more than 80 % of drug release was achieved within 180 min with 200 mg dose of CBZ. From the present investigations it is concluded that the CBZ dissolution rate is dependent on dose as well as pH dissolution media. Moreover, innovative formulation strategies such as time release pellets, short term sustained release dosage forms may provide better dissolution profile and bioavailability.