Determining the Best Poloxamer Carrier for Thiocolchicoside Solid Dispersions.

OBJECTIVES: The aim of this study of this study was to discover the best poloxamer as a solid dispersion carrier for thiocolchicoside (TCS). MATERIALS AND METHODS: The compatibility of TCS with excipients was studied by differential scanning colorimetry and fourier transform infrared spectroscopy. Different formulations of solid dispersions (SDs) were made with poloxamer carriers, i.e. poloxamer-108, poloxamer-188, poloxamer-237, poloxamer-338, and poloxamer-407 were made by taking TCS:poloxamer in ratios of 1:1, 1:2, 1:4, and 1:6. The SDs were made by a novel microwave fusion method and compressed using an 8-station tablet compression machine. The fabricated SD tablets were characterized by physicochemical constraints and drug release rates. The release of TCS from the prepared SDs was later analyzed by kinetic models. RESULTS: TCS was observed to be compatible with the poloxamer carriers. The SD formulations showed satisfactory physicochemical constraints and TCS release following first-order release. CONCLUSION: Among the poloxamer carriers used, poloxamer-188 was the best for increasing the solubility and release rate of TCS from the SDs.

Sustainable green synthesis of silver nanoparticles by using Rangoon creeper leaves extract and their spectral analysis and anti-bacterial studies.

The plant-based biological molecules possess exceptionally controlled assembling properties to make them suitable in the synthesis of metal nanoparticles. In the present study, an efficient simple one-pot method was employed for the synthesis of silver nanoparticles (SNPs) from the Rangoon creeper (RC) aqueous leaf extract. Biomolecules present in the leaf extract play a significant role as reducing agent as well as capping agent in the formation of RC-SNPs. The formation of RC-SNPs was confirmed by using several analytical techniques such as Fourier-transform infrared spectroscopy and ultraviolet-visible spectrophotometer studies. The presence of a sharp surface plasmon resonance peak at 449 nm showed the formation of RC-SNPs. X-ray diffraction analysis showed the crystalline nature of the RC-SNPs with a face-centred cubic structure. Elemental analysis of RC-SNPs was done by using energy-dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy. The morphology of RC-SNPs was examined by transmission electron microscopy (TEM) in the nano range 12 nm, and thermogravimetric-differential thermal analysis demonstrated the mechanical strength of RC-SNPs at various temperatures. The authors' newly synthesised RC-SNPs exhibited significant anti-bacterial activity against Staphylococcus aureus and Escherichia coli.

Impact of Pharmacist-directed Counseling and Message Reminder Services on Medication Adherence and Clinical Outcomes in Type 2 Diabetes Mellitus.

INTRODUCTION: Medication nonadherence is the most common issue observed in the management of diabetes because of complex and lifelong therapy. The study aimed to assess the effect of pharmacist-directed counseling and daily text message reminder on medication adherence and clinical profile of patients with type II diabetes. MATERIALS AND METHODS: This prospective, open-labeled, randomized control trial was carried out in outpatient medical department of a secondary care referral hospital. A total of 330 patients who met study criteria were enrolled and randomized into an intervention group (n = 165), received counseling and daily messages about medication intake and control group (n = 165), and usual care by physician. Medication adherence and clinical outcomes such as glycosylated hemoglobin (HbA1C), systolic blood pressure (SBP), low-density lipoprotein (LDL) cholesterol, triglyceride (TG) levels, and body mass index (BMI) were recorded at baseline and follow-up visits. Two-sample Wilcoxon rank sum test was used to compare the mean difference of medication adherence and paired t-test was used to compare clinical outcomes. RESULTS AND DISCUSSION: The mean age of intervention and control groups were 57.1 ± 8.55 and 58.5 ± 8.53 years, respectively. The mean difference of medication adherence from baseline to second follow-up visit was significantly more in intervention group (12.2 ± 7.1%) compared to that in control group (0.75 ± 10.2 %) with a P < 0.001. From baseline to second follow-up visit, HbA1C (7.79 ± 0.67 to 6.91 ± 0.83 %), SBP (136.75 ± 20.09 to 126.23 ± 18.22 mm Hg), and LDL cholesterol (104.14 ± 26.23 to 98.29 ± 20.87 mg/dL) levels were significantly reduced in intervention group compared to that in control group with a P < 0.01. No significant improvement was observed in TG (169± 33.71 to 168 65 ± 33.90 mg/dL) and BMI (27.9 ± 4.21 to 27.1 ± 3.12 Kg/m2) levels from baseline to second follow-up visit. CONCLUSION: Pharmacist-directed patient counseling combined with message reminder showed a greater effect on the improvement of medication adherence and control of glycemia, blood pressure, and lipid profile in diabetes.

Anti-proliferative and anti-malarial activities of spiroisoxazoline analogues of artemisinin.

A series of spiroisoxazoline analogues of artemisinin was synthesized by employing 1,3-dipolar cycloaddition between various in situ generated nitrile oxides and artemisitene. All the synthesized compounds were tested for their anti-proliferative and anti-malarial activities. Among the compounds tested, compound 11a was found to be potent against the HCT-15 cancer cell line with IC50 = 4.04 µM when compared to 5-fluorouracil (IC50 = 35.53 µM). DNA cell cycle analysis shows that 11a was inhibiting cell proliferation at the G2/M phase. Compound 11b was found to be most active against Plasmodium falciparum with IC50 = 0.1 µM and also blocked host hemoglobin hydrolysis by the falcipain-3 receptor. It was demonstrated to have better dynamics of parasite killing efficiency than artemisinin. Molecular docking studies revealed that these compounds interacted with falcipain-3 receptor sites.

Nephro-protective action of P. santalinus against alcohol-induced biochemical alterations and oxidative damage in rats.

The present study investigated the antioxidant potential of P. santalinus heartwood methanolic extract (PSE) against alcohol-induced nephro-toxicity. The results indicated an increase in the concentration of kidney damage plasma markers, urea and creatinine with a concomitant decrease in the concentration of uric acid in alcohol-administered rats. A significant decrease in plasma electrolytes and mineral levels with increased kidney thiobarbituric acid reactive substances (TBARS) and nitric oxide (NOx) levels was also observed. PSE treatment to alcohol-administered rats effectively prevented the elevation in TBARS and NOx levels. Decreased activity of Na+/K+-ATPase in alcohol administered rats was brought to near normal levels with treatment of PSE. Chronic alcohol consumption affects antioxidant enzymatic activity and reabsorption function of the kidney which is evident from the decreased level of GSH as well as the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione s-transferase (GST). However, treatment with PSE to alcohol-administered rats significantly enhanced these enzymatic activities and reduced glutathione (GSH) content close to normal level. Alcohol-induced organ damage was evident from morphological changes in the kidney. Nevertheless, administration of PSE effectively restored these morphological changes to normal. The flavonoid and tannoid compounds might have protective activity against alcohol-induced oxidative/nitrosative stress mediated kidney damage.

Altered pharmacokinetics and pharmacodynamics of repaglinide by ritonavir in rats with healthy, diabetic and impaired hepatic function.

BACKGROUND: Ritonavir is an antiretroviral drug to treat HIV AIDS and inhibits cytochrome P450 3A4. To treat diabetes mellitus in HIV, repaglinide is coadministered with ritonavir in the clinic. Multiple cytochrome P450 (CYP) isoforms are involved in the metabolism of repaglinide like CYP2C8 and CYP 3A4. In order to predict and understand drug-drug interactions of these two drugs, the pharmacokinetics and pharmacodynamics (PK/PD) of repaglinide and ritonavir were studied in normal, diabetic and hepatic impaired rats. The purpose of the study was to assess the influence of ritonavir on the PK/PD of repaglinide in rats with normal, diabetic and impaired hepatic function. METHODS: Human oral therapeutic doses of ritonavir and repaglinide were extrapolated to rats based on the body surface area. Ritonavir (20 mg/kg, p.o.), alone and along with repaglinide (0.5 mg/kg, p.o.), was given to normal, diabetic and hepatic impaired rats, and the PK/PD were studied. RESULTS: The pharmacokinetic parameters like peak plasma concentration (Cmax), area under the plasma concentration time profile (AUC) and elimination half life of repaglinide were significantly (p<0.0001) increased when compared to repaglinide control rats. The repaglinide clearance (CL) was significantly (p<0.0001) decreased in the presence of ritonavir treatment. In the presence of ritonavir, repaglinide hypoglycemic activity was increased significantly (p<0.0005) when compared with repaglinide control group. CONCLUSIONS: The significant difference in the PK/PD changes have been due to the increased plasma exposure and decreased total body clearance of repaglinide, which may be due to the inhibition of the CYP P450 metabolic system and organic anion-transporting polypeptide transporter by ritonavir.

Stability-indicating RP-HPLC method for the quantitative analysis of perindopril erbumine in tablet dosage form.

A specific, stability-indicating reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed and validated for the estimation of perindopril erbumine (PDE) in tablet dosage form. The HPLC method showed adequate separation of PDE from its degradation products. The separation was achieved on a Phenomenex Luna C18 column (250 × 4.6 mm × 5 µm) using a mobile phase composition of 0.2% trifluoroacetic acid buffer and acetonitrile in the ratio of 60:40 (pH adjusted to 3 with ammonia) at a flow rate of 1 mL/min. The injection volume was 20 µL and the wavelength of detection was kept at 215 nm. Stress studies were performed with 1 mg/mL of each drug, starting with mild conditions and followed by stronger conditions to achieve sufficient degradation at approximately 5-20%. The linearity of the proposed method was investigated in the range of 2.5 to 50 µg/mL for PDE. The limits of detection and quantification were found to be 0.75 and 2.3 µg/mL, respectively.

Development and Validation of a Stability-Indicating Assay of Etofenamate by RP-HPLC and Characterization of Degradation Products.

A validated stability-indicating RP-HPLC method for etofenamate (ETF) was developed by separating its degradation products on a C18 (250 mm × 4.6 mm 5 µm) Qualisil BDS column using a phosphate buffer (pH-adjusted to 6.0 with orthophosphoric acid) and methanol in the ratio of 20:80 % v/v as the mobile phase at a flow rate of 1.0 mL/min. The column effluents were monitored by a photodiode array detector set at 286 nm. The method was validated in terms of specificity, linearity, accuracy, precision, detection limit, quantification limit, and robustness. Forced degradation of etofenamate was carried out under acidic, basic, thermal, photo, and peroxide conditions and the major degradation products of acidic and basic degradation were isolated and characterized by (1)H-NMR, (13)C-NMR, and mass spectral studies. The mass balance of the method varied between 92-99%.

Antiinflammatory, antinociceptive and antioxidant activities of Phyllanthus acidus L. extracts

Objective: To evaluate analgesic, anti-inflammatory and in vitro antioxidant potential and determine total phenolic, total flavonoid content of leaves extracts of Phyllanthus acidus, a folk medicinal plant of India. Methods: Anti-inflammatory activity was evaluated using carrageenan induced paw oedema, cotton pellet induced granuloma, membrane stabilizing activity method. Analgesic activity of the extracts was estimated against acetic acid induced writhing, tail immersion method, formalin test. Free radical scavenging and antioxidant potential of the extracts of Phyllanthus acidus leaves was performed using several in vitro and ex vivo assay models. Total phenolic and total flavonoid contents of the extracts were determined using standard chemical methods. Results: The extracts exhibited significant anti-inflammatory and analgesic activities at dose dependent manner. Methanol extract at a dose of 500 mg/kg showed superior activity which was comparable with the standard drugs. Ethyl acetate extract showed moderate activity while petroleum ether extract showed least activity. Total phenolic and total flavonoid content in methanol extract were 73.08±0.682 mg GAE/g and 61.28±0.062 mg QE/g respectively. The extracts possess significant antioxidant activity, methanol extract showed highest IC50 value. The contents of flavonoids and phenolic compounds could be correlated with the antioxidant, analgesic and anti-inflammatory activities observed for Phyllanthus acidus leaves. Conclusion:Our findings suggest that Phyllanthus acidus contains potential antioxidant, analgesic and anti-inflammatory compounds which could be tested as drug candidates against oxidative stress, pain and inflammation related pathological diseases.