Nadeem Irfan Bukhari

Metronidazole leads to enhanced uptake of imatinib in brain, liver and kidney without affecting its plasma pharmacokinetics in mice.

Objectives  The pharmacokinetic interaction between metronidazole, an antibiotic–antiparasitic drug used to treat anaerobic bacterial and protozoal infections, and imatinib, a CYP3A4, P‐glycoprotein substrate kinase inhibitor anticancer drug, was evaluated.

Medicine utilisation and pricing in Malaysia: The findings of a household survey

The objectives of this study were to identify the most commonly used medicines for mainly prevalent ailments and to compare retail sector prices (RSPs), public sector prices (PSPs) and international reference prices (IRPs). A convenient sampling method was employed to survey 33 households in a metropolitan city. Each family was followed once a week for eight weeks to observe their diseases and medication usage. The RSPs and PSPs for per unit doses and defined daily doses (DDDs) were compared with the IRPs. The most common ailments identified were cardiovascular and endocrine disorders followed by central nervous system and musculoskeletal disorders. Accordingly, the most common drugs used were for the treatment of the above ailments. Among 81 commonly used medicines, 63 were branded and 18 were generic. Of the 81 drugs, 26 were essential drugs. Angiotensin-converting enzyme (ACE) inhibitors, beta-blockers and calcium channel blockers were among the most commonly used medicines. The differential between the prices of branded medicines and IRPs were found to be remarkable. This study further revealed that the majority of patients also used traditional medicines and nutritional supplements alongside their modern medicines. Wide variations were observed in RSPs and IRPs, warranting critical evaluation, regulation and emphasis on the economic aspects of drug policy. Widespread use of branded medicines in the absence of a national health insurance programme can lead to high out-of-pocket expenditures. Concomitant use of traditional medicines and nutritional supplements may have drug interaction potential, invoking detailed investigation for relevance.

Folate grafted thiolated chitosan enveloped nanoliposomes with enhanced oral bioavailability and anticancer activity of docetaxel

Folate grafted and thiolated chitosan was synthesized and wrapped on the surface of mixed phosphatidylcholine based nanoliposomes (NLs) to improve the oral absorption and targeted pharmacological activity of anti-cancer drugs against breast cancer. In this study, a chitosan derived thiomer, having intrinsic properties of P-glycoprotein (P-gp) efflux pump inhibition, mucoadhesion and controlled drug release at a target site, was exploited to improve the performance of docetaxel (DTX) loaded NLs for better oral pharmacokinetics, targeted anti-cancer activity, liposomal stability and the physical characteristics of NLs. Thiomer enveloped nanoliposomes (ENLs) and bare nanoliposomes (NLs) were synthesized with the ingredient ratio pre-determined via Response Surface Methodology (RSM) plots by Design Expert® software. ENLs and NLs were thoroughly characterized for their surface chemistry, particle size, zeta potential, PDI, encapsulation efficiency, stability and release profile. ENLs were spherical in shape with a particle size of 328.5 ± 30 nm, a positive zeta potential of 18.81 ± 2.45 and a high encapsulation efficiency of 83% for DTX. Controlled release of DTX from formulations was observed for over 72 h for each formulation. The presence of thiol groups at the surface of the ENLs resulted in higher swelling and in situ gelling properties compared to the corresponding NLs. Furthermore, ENL/mucin mixtures showed a time dependent increase in viscosity for up to 12 h, leading to a 19.07-fold increased viscosity. Ex vivo permeation and P-glycoprotein inhibiting properties, studied in rats small intestine, showed a 9.6-fold higher permeation and 13-fold enhancement of DTX in the presence of ENLs. In vitro cytotoxicity studies indicated that the ENLs can efficiently kill MD-MB-231 breast cancer cells with 200 fold lower IC50 values than DTX alone as a positive control. The pharmacokinetic study revealed that the ENLs significantly improved the oral bioavailability of DTX i.e. up to 13.6 fold as compared to an aqueous dispersion of DTX. Therefore, these enveloped hybrid nanoliposomes (ENLs) have the potential to be developed as useful nanocarriers for efficient oral delivery and breast cancer management using DTX.

Quantification of residual crystallinity in ball milled commercially sourced lactose monohydrate by thermo-analytical techniques and terahertz spectroscopy.

The quantification of crystallinity is necessary in order to be able to control the milling process. The use of thermal analysis for this assessment presents certain challenges, particularly in the case of crystal hydrates. In this study, the residual crystallinity on ball milling of lactose monohydrate (LMH), for periods up to 90min, was evaluated by thermo-analytical techniques (TGA, DSC) and terahertz spectroscopy (THz). In general, the results from one of the DSC analysis and the THz measurements agree showing a monotonous decrease in relative residual crystallinity with milling time (∼80% reduction after 60min milling) and a slight increase at the 90min time point. However, the estimates from TGA and two other methods of analyzing DSC curve do not agree with the former techniques and show variability with significantly higher estimates for crystallinity. It was concluded that, the thermal techniques require more complex treatment of the data in the evaluation of changes in crystallinity of a milled material (in particular to account for the de-vitrification and mutarotation of the material that inevitably occurs during the measurement cycle) while the analysis of THz data is more straightforward, with the measurement having no impact on the native state of the material.

Advances in nano-delivery systems for doxorubicin: an updated insight

Abstract Doxorubicin (DOX) is the most effective chemotherapeutic drug developed against broad range of cancers such as solid tumours, transplantable leukemias and lymphomas. Conventional DOX-induced cardiotoxicity has limited its use. FDA approved drugs i.e. non-pegylated liposomal (Myocet®) and pegylated liposomal (Doxil®) formulations have no doubt shown comparatively reduced cardiotoxicity, but has raised new toxicity issues. The entrapment of DOX in biocompatible, biodegradable and safe nano delivery systems can prevent its degradation in circulation minimising its toxicity with increased half-life, enhanced pharmacokinetic profile leading to improved patient compliance. In addition, nano delivery systems can actively and passively target the tumour resulting increase in therapeutic index and decreased side effects of drug. Foreseeing the need of a comprehensive review on DOX nanoformulations, in this article we for the first time have given an updated insight on DOX nano delivery systems.

Once daily controlled release matrix tablet of Prochlorperazine maleate: Influence of Ethocel® and/or Methocel® on in vitro drug release and bioavailability

Context: Controlled release (CR) matrix tablet of Prochlorperazine maleate was developed to improve its patient compliance. Methods: Tablet formulations F1, F2 and F3 based on different concentrations of Methocel® K100 LV-CR Premium, were compacted by direct compression method while tablet formulations F4, F5 and F6, based on distinct blends of Methocel® K100 LV-CR Premium and Ethocel® Standard 7FP Premium, were compressed by flow-bound dry granulation-slugging method. The prepared powder mixtures, granules and tablets were evaluated for their physicochemical performance. Bioequivalence study of the optimized test tablet versus reference-conventional Stemitil® tablet was conducted on rabbits, using HPLC-UV system at λmax 254 nm. Results: The test tablet, containing 28% Methocel® and 58% Ethocel® (F6) exhibited desired zero order kinetics for 24 h and was found stable at accelerated storage conditions for 6 months. In vitro drug release rate decreased as the Ethocel® content in the blend was increased, perhaps due to slower penetrability of water. Hydrodynamic conditions and hardness of tablets could not affect drug release kinetics. The tablet displayed significantly (p < 0.05) optimized peak drug concentration-Cmax (45 ± 3.42 vs. 64.5 ± 4.03), extended half life-t1/2 (16.071 ± 3.97 vs. 5.257 ± 1.314 h) and bioequivalence to the reference tablet taken three times a day (1409 ± 15 ng·h/mL vs. 1346 ± 23 ng h/mL). The tablet showed strong Level A correlation (R2 = 0.8458) between drug absorbed in vivo and drug released in vitro. Conclusions: The developed tablet may be adopted by pharmaceutical industry to improve patient compliance of the Prochlorperazine maleate.

Performance evaluation on effect of pre-sonication on nanoparticulates during wet nano-milling of drugs

Nano-sizing of drug particle size has been identified as a potentially effective method to increase solubility and hence drug effectiveness. By nanomilling, stable nano-scale particulates can be prepared which have improved physical properties. Nanoparticulates of poorly water-soluble drugs can be prepared by milling of drugs into nano range and achieve optimal stability condition. In this study, effect of pre-sonication followed by wet grinding was assessed on the particle sizes of griseofulvin and ketoconazole in dispersions containing surfactants. The sizes of drugs particulates were reduced to less than 200nm in size with a Polydispersity Index (PDI) below than 1.0 when pre-sonication and nanomilling were applied consecutively.

Investigation of in vivo antioxidant activity of Euphorbia helioscopia latex and leaves methanol extract: a target against oxidative stress induced toxicity

OBJECTIVE To evaluate in vivo antioxidant activity of latex and leaves methanol extract of Euphorbia helioscopia using mice as experimental animals. METHODS The plant was collected, identified, dried under shade, ground to fine powder and extraction was done. Latex was collected in dried bottles by cutting the stem. Oxidative stress was induced in mice with acute toxic dose of paracetamol administered intrperitoneally. Latex and leaves methanol extract (600 and 1 200 mg/kg) orally, once a day, were given to mice for two weeks. Then oxidative stress biomarkers were measured in tissue homogenates and serum. RESULTS Leaves methanol extract exhibited prominent in vivo antioxidant effect as compared to latex. Results showed significant rise in antioxidant enzymes (catalase, superoxide dismutase and glutathione) levels at 1 200 mg/kg dose of extract. Thus, extract helped to detoxify the free radicles by increasing antioxidant enzymes levels. Malondialdehyde value decreased significantly with extract (1 200 mg/kg) which was indicator of extracts power to inhibit the generation of free radicals. Extract (1 200 mg/kg) exhibited maximum cure against stress induced changes in liver, kidney, lipid profile parameters and complete blood count. CONCLUSIONS Leaves methanol extract of Euphorbia helioscopia raised antioxidant enzymes levels in mice. It showed hepatorenal-curative effect, hypolipidemic effect and hemostasis potential. Thus, it can help the biological systems to fight against stress induced pathological conditions.

The effect of preparation parameters on the size and morphology of PLGA-based nanoparticles

Nanoparticles now have various pharmaceutical and biomedical applications due to the many advantages such as improvement in drug bioavailability, ability to cross barriers after oral and parentral administration, and being an excellent drug carrier for insoluble drugs. However, size and morphological characteristics of nanoparticles are critical for drug release in the body, warranting understanding the parameters controlling the above characteristics. This paper describes, firstly, preparation parameters to optimize the size of polylactic-co-glycolic acid (PLGA)-based nanoparticles, and secondly, study the morphology of the same nanoparticles, formed by the emulsion solvent evaporation technique. The solvent evaporation technique involves an aqueous phase containing polyvinyl alcohol (PVA) as a stabilizing agent. After washing, the samples were freeze-dried and analyzed using particle size analyzer and scanning electron microscope. The preparation parameters studied included; homogenizing speed, homogenizing time, stabilizer concentration and temperature.

Disposition kinetics of erythromycin in normal and experimentally-induced febrile rabbits

SummaryThe disposition kinetics of erythromycin were determined in normal and endotoxin-induced febrile rabbits following intravenous injection of a single dose of 10 mg/kg body weight. In febrile rabbits, body weight, blood pH, total lipids and total proteins in plasma remained unchanged, packed cell volume, albumin and the albumin/globulin ratio reduced while glucose and globulins increased significantly. The mean plasma drug concentration was lower under febrile conditions at all the sampling times except at 480 and 720 min after drug administration where the levels remained the same. The values for t1/2elim and MRT of the drug were observed to be prolonged while that of the Clt reduced and Vd increased in the febrile rabbits. The febrile condition resulted in an alteration in the disposition kinetics of erythromycin suggesting an adjustment of the dosage under febrile conditions.