Pharmacological activities of a novel phthalic acid ester and iridoid glycoside isolated from the root bark of Anthocleista vogelii Planch

@#In this study, a novel phthalic acid ester (1) and a known iridoid glycoside (2) were isolated from the root bark of Anthocleista vogelii. The structures of the novel compound and iridoid glycoside were elucidated on the basis of their chemical and spectral data (UV, FT-IR, EI-MS, 1D and 2D NMR) and found to be phthalic acid ester, 4-ethyl-6-propyl-4,5,6,7-tetrahydro- 3H-2,8-benzodioxacycloundecine-1,9-dione (1) and sweroside (2). The compounds were evaluated for their in vitro inhibitory activities against pancreatic lipase, α-amylase and α- glucosidase, and in vivo laxative activity in rats. The metabolite phthalic acid ester (1) exhibited moderate inhibitory activity against pancreatic lipase (IC50 = 24.43 ± 0.096 μg/mL) and relatively good activity against α-glucosidase (IC50 = 10.28 ± 0.015 μg/mL). Sweroside (2) displayed weak activity against α-glucosidase (IC50 = 40.28 ± 0.063 μg/mL) but significantly (p<0.05) increased the feacal output of the treated animals compared to the normal and sodium picosulfate controls.

Impact of pharmacist's intervention on disease related knowledge, medication adherence, HRQoL and control of blood pressure among hypertensive patients

The present study was aimed to evaluate the effect of educational intervention provided to the patients of hypertension through pharmacist with the goal to improve knowledge about hypertension, adherence to prescribed medicines, blood pressure control and HRQoL [Health Related Quality of Life]. A total of 384 patients were assigned randomly into 2 groups including intervention and control groups each having 192 patients. Urdu versions of knowledge questionnaire regarding hypertension, medication adherence scale [MMAS-U] by Morisky and EuroQol scale [EQ-5D] were utilized. Each patient's blood pressure was measured. After educational intervention, an increase was found in mean knowledge score about hypertension [18.18 +/- 4.00], adherence score [5.89 +/- 1.90], HRQoL score [0.73 +/- 0.12] and Visual Analogue Scale [VAS] score [69.39 +/- 5.90] among the IG. The blood pressure control also improved and lower systolic [131.81 +/- 10.98 mmHg] and diastolic blood pressures [83.75 +/- 6.21 mmHg] were observed among the patients of IG. This study showed that educational programs are useful for patients in increasing patient's levels of knowledge about hypertension, improving adherence to prescribed medication and enhancing blood pressure control. This increase is in turn accountable to improve HRQoL

Cross-linked guar gum and sodium borate based microspheres as colon-targeted anticancer drug delivery systems for 5-fluorouracil

The aim was to prepare cross linked polymer of 5-fluorouracil loaded microspheres containing guar gum and sodium borate for colon-targeted drug delivery systems. Micro spheres were prepared using emulsification cross linking method. The influence of drug polymer ratio, cross linker agent concentrations and cross linking timing on in vitro drug release and characteristics in terms of drug loading, entrapment efficiency and yielding percentage were investigated. The optimum drug loading, entrapment efficiency and percent yield were obtained from formulations with the lowest content of cross linker agent over 2 h of cross linking timing but with the highest drug to polymer ratio 1:11. The optimum in vitro drug release was obvious upon decreasing drug to polymer ratio up to 1:09, resulting in 81.5% drug release over 24 h. In conclusion, micro spheres composed of gaur gum and sodium borate can delay and control the release of 5-fluorouracil over 24 h. Thus, further in vivo studies are suggested for final assessment

Suitability of Gelucire 50/13 for controlled release formulation of salbutamol sulphate

Gelucire 50/13 [G50/13] was assessed to develop controlled release formulation of salbutamol sulphate [SBL] a highly water soluble drug by semisolid matrix filling capsule technique. Drug release profiles of SBL release by using G50/13 and its blends with other hydrophilic or hydrophobic materials were investigated. Lipid matrix formulations prepared with increasing amount of polymer showed a substantial decrease in release rate of the drug while increasing drug amount in fixed polymer concentration did not significantly affect the release profile. Polyethylene glycol 6000 caused an increased water uptake resulting in fast erosion of the matrix whereas cetostearyl alcohol and stearic acid caused retardation in drug release. These findings confirm that a considerable amount of Gelucire is required alone or in combination with hydrophobic substances in order to sustain the release profiles of water soluble drugs. More linear profile was obtained by using matrix comprising Gelucire/stearic acid blend in more than 85% that was comparable to standard, Ventolin SR tablet. The test formulation showed a significant decrease at pH 1.0 and the drug release rate increased at high stirring speed. Moreover, short term stability of controlled release test formulation indicated slight increase in dissolution rate at high temperature

Defining prescribing errors in general practice for the hospitals in Pakistan

To reach consensus on a definition of prescribing errors and different scenarios representing prescribing error situations in general practice by a Pakistani panel of expert judges. Later this definition and scenarios will be used for evaluating prescribing practices in hospitals. The study was designed to be conducted in a Two-Round Delphi Technique though a questionnaire to be delivered hand-by-hand to each member of the panel. This was a prospective at various of judges hospitals study conducted in Lahore and Bahawalpur from May 2006 to July 2006. A questionnaire in a two-round Delphi technique was followed to gauge consensus on a definition and 46 scenarios proposed to be representing prescribing error situations. Consensus was reached to agree upon a definition of prescribing errors, 33 [71.7%] scenarios were considered prescribing errors, 8 [17.4%] scenarios were excluded and 5 [10.9%] were partially agreed upon to be considered depending on the individual situation. The Pakistani panel of expert judges agreed upon the definition and scenarios to be considered prescribing errors. The definition and scenarios can also be used for future research on prescribing errors in Pakistani hospitals

Comparative bioavailability and in vitro in vivo correlation of two sustained release brands of theophylline: tablets and pellets

To investigate the influence of dosage forms on bioavailability, a randomized single-dose crossover study under fasting conditions was conducted using two commercially available sustained release products, Quibron SR tablets and Respro-SR pellets filled Capsules containing 300mg theophylline. A group of 12 healthy, male human subjects participated in this study. Serial blood samples were collected at 0, 1, 2, 3, 4, 6, 8, 10, 12 and 24 h. Theophylline was measured by high-performance liquid chromatography while absorption profiles were derived using Wagner-Nelson equation. The bioavailability of Quibron SR tablets was compared with Respro-SR pellets filled Capsules 300 mg using pharmacokinetic parameters C[max], T[max], AUC0-t, and AUC0-8. In addition, the 90% confidence interval [CI] for the ratio of logarithmic transformed C[max] and AUC0-8 was also used to determine bioequivalence. The T/R [test/reference] ratio of Quibron SR tablets was quite close to the prescribed limits of bioequivalence i.e. 80-125%. No st atistically difference was observed between the log transformed AUC[0-infinity] [P = 0.971] values as well as log transformed C[max] values [P = 0.854] indicating bio-availability and the extent of absorption of two brands were comparable. Moreover, the value of correlation coefficients for% in vivo absorption versus% in vitro dissolution of the two products was calculated to be 0.9533 for Respro-SR capsule and 0.9789 for Quibron-SR tablets

Oral sustained release pellets of diltiazem HCL with Kollicoat SR30

An aqueous dispersion of polyvinyl acetate [Kollicoat SR30] was selected for the development and in vitro evaluation of diltiazem sustained release pellets. Five coating levels based on theoretical weight gains of 7, 8, 9, 10 and 11% were examined onto drug pellets using fluidized bed technique. Coated pellets were thermally treated at 37°C, 40°C, 50°C and 60°C for 24 hours. In vitro dissolution tests were performed in distilled water while selected batches were compared to the release data in test media having pH 1, 4 and 7. The release profiles of coated pellets were found to be inversely proportional to the thickness of Kollicoat SR30 coat and desirable controlled release characteristics could be achieved by manipulating the coating levels. Plasticizers [propylene glycol/triethyl citrate] and anti-adherent [magnesium stearate] in the formulation of coated pellets reduced the release rates. Thermally treated pellets also showed reduction in the release rates at 60°C compared to initial release profile at 37°C. However, the drug release rates was found to be fairly independent of dissolution media [pH 1,4 and 7]

Simultaneous HPLC-UV quantification of diltiazem and N-demethyldiltiazem in human plasma

A simple and sensitive reversed phase high-performance liquid chromatographic method was developed for simultaneous quantification of diltiazem HCl and its major metabolite N-demethyldiltiazem in human plasma. The method involves one step solvent extraction of diltiazem, N-demethyldiltiazem and the internal standard, verapamil with n-hexane and diethyl ether [50:50 v/v]. The mobile phase comprised 0.1 M ammonium dihydrogen phosphate-acetonitrile [62:38 v/v] and triethylamine [0.08%] was added before the pH was adjusted to 5.9 with 85% phosphoric acid. Analysis was run at a flow rate of 1.0 ml/min at a detection wavelength of 238 nm. The completion time for assay was not more than 10 minutes and lower limit of quantification was 5 ng/ml. The calibration curve for diltiazem and its metabolite was linear over a concentration range of 5-200 ng/ml and average recovery was about 90%. The coefficient of variation and percent error values of the assay method within and between days were all less than 10%

Diltiazem release from eudragit NE40 coated pellets and effects of themal treatment

A film coat for diltiazem pellets was applied with aqueous dispersion of Eudragit NE40 using bottom spray Fluidized-bed coater. The effects of thermal treatment, dissolution media and ionic strength of media on drug release from the pellets were evaluated. Coated pellets were treated at 37°C, 40°C, 50°C and 60°C for 24 hours. Thermally treated pellets showed slight reduction in the release rates at 50°C and 60°C compared to initial release profile at 37°C. Curing or thermal treatment of the coat at an appropriate temperature and length of time was found essential to achieve complete coalescence of the polymer particles such that the rate of drug release was stable during prolonged storage. Diltiazem release was fairly independent of pH and the ionic strength of the dissolution media. However, the release rates were slightly decreased with increasing molar concentrations of sodium chloride in the buffer media

Simultaneous HPLC quantification of diltiazem and N-demethyldiltiazem in plasma

A simple and sensitive reversed phase high-performance liquid chromatographic method was developed for simultaneous quantification of diltiazem and its major metabolite N-demethyldiltiazem in human plasma. The method involves one-step solvent extraction of diltiazem, N-demethyldiltiazem and the internal standard, verapamil with n-hexane and diethyl ether [50:50 v/v]. The mobile phase comprised 0.1M ammonium dihydrogen phosphate-acetonitrile [62:38 v/v] and triethylamine [0.08%] was added before the pH was ajusted to 5.9 with 85% phosphoric acid. Analysis was run at a flow rate of 1.0 ml/mm at a detection wavelength of 238 nm. The completion time for assay was not more than 10 minutes and lower limit of quantification was 5 ng/ml. The calibration curve for diltiazem and its metabolite was linear over a concentration range of 5-200 ng/ml and average recovery was about 90%. The coefficient of variation and percent error values of the assay method within and between day were all less than 10%

Improved high performance liquid chromatographic analysis of diltiazem in human plasma

A simple high-performance liquid chromatographic method was developed for determination of diltiazem in human plasma. Diltiazem and the internal standard, verapamil, were extracted from plasma samples using mixture of n-hexane and diethyl ether. The mobile phase was 0.1M ammonium dihydrogen phosphate - acetonitrile [62:38 v/v]. Triethylamine [0.08% v/v in the mobile phase] was added before the pH was adjusted to 5.9 with 85% phosphoric acid. Analysis was run at a flow rate of 1.0 ml/min at a detection wavelength of 238 nm. The method was specific and sensitive with a detection limit of 2.5 ng/ml at a signal-to-noise ratio of 3:1. The limit of quantification was set at 5 ng/ml. The calibration curve was linear over a concentration range of 5-160 ng/ml. Mean recovery value of the extraction procedure was about 90%, while the within and between day coefficient of variation and percent error values of the assay method were less than 10%

Differential scanning calorimetry and surface morphology studies on cated pellets using aqueous dispersions

The present study was conducted to examine the physicochemical changes during passage of drug through polymeric membranes and observe the surface morphology features of the coated pellets using scanning electron microscopy [SEM]. Drug solution was first sprayed around inert pellets to form drug-layered pellets that were coated with two commercial aqueous dispersions namely, Eudragit NE30 and Kollicoat SR30 using bottom-spray fluidized bed technique. Differential scanning calorimetry [DSC] confirmed that no interactions existed between drug and polymers. Small peak of drug was observed in the DSC thermograms of Eudragit NE30 coated pellets indicating that small amount of drug was still present in the polymeric membrane after dissolution. Views of SEM revealed as the coating levels of two types of aqueous dispersions were increased the surface of the pellets become more uniform and compact. Therefore, the diffusion length for dissolution medium to enter the drug layer and dissolved drug to diffuse out would be increased at higher coating levels. The polymer surface of coated pellets after 12 hours dissolution testing seemed to be shrunk and size of the pellets were also reduced indicating the depletion of reservoir layer

In vivo performance of controlled release pellets of dil tiazem HCI

The test formulation of controlled release diltiazem pellets was evaluated in vivo, in comparison with Herbesser SR. Six healthy volunteers participated in the study, conducted according to a randomized, two-way crossover study design. The preparations were compared using the pharmacokinetic parameters plasma concentration-time curve [AUC], peak plasma concentration [Cmax] and time to reach maximum plasma concentration [Tmax] were estimated from the plasma concentration-time profiles for each volunteer. The test formulation was found to be comparable with the Herbesser SR in the extent of bioavailability but differ in the rate of absorption, the test formulation being less sustained. No lag time was observed in any of the volunteers indicating that both formulations started to release their drug content immediately upon rupture of the capsule but in sustained manner. Moreover, the values of pharmacokinetic parameters obtained were comparable to those reported in the literature

Bioequivalence of two brands of piroxicam 20 mg capsule in healthy human volunteers

An open randomized, two-way crossover study was carried in 12 healthy volunteers. The two commercial brands used were Uphaxicam [Upha, Malaysia] as test and Feldene [Pfizer, France] as reference product. The drug was administered to each subject with 240 ml of water after an overnight fasting in two treatment days separated by three weeks washout period. The bioavailability was compared using the parameters total area under the plasma concentration time curve [AUC [0-infinity]], peak plasma concentration [C max] and time to reach maximum plasma concentration [T max]. No statistically significant difference was observed between the values of two products in AUC [0-infinity] and C max while significant difference was found in T max However, the 90% confidence interval for the ratio of logarithmic-transformed AUC[0-infinity] and C max values of Uphaxicam over those of Feldene was found to lie between 0.92- 1.03 and 0.91-1.00, respectively, being within the acceptable bioequivalence limit of 0.8-1.25. Based on this data, it is concluded that both formulations are bioequivalent and interchangeable in medical practice