An improved and validated LC method for resolution of bicalutamide enantiomers using amylose tris-(3,5-dimethylphenylcarbamate) as a chiral stationary phase

An improved HPLC method for determination of enantiomeric purity of bicalutamide in drugs and pharmaceuticals was developed and validated. Baseline separation with resolution >/=6.0 was achieved within 10 min on Chiralpak AD-H (250 mm x 4.6 mm; particle size 5 microm) column using n-hexane:2-propanol (65:35 v/v) as mobile phase at a flow rate of 1.0 ml/min at 25 degrees C. The detection was made at 270 nm using UV detector while a polarimetric detector connected in series was used for identification of enantiomers. The effects of 2-propanol, ethanol and temperature on enantioselectivity and resolution of enantiomers were evaluated. The method was validated in terms of accuracy, precision and linearity in the range of 10-250 microg/ml and the r(2) was >0.9999. The recoveries were 99.68-100.25% with <1% R.S.D. The limits of detection (LOD) and quantification (LOQ) of enantiomers were (2.4, 3.0 and 7.6, 9.3) x 10(-8)g/ml for (S)-(+)-BCT and (R)-(-)-BCT enantiomers, respectively. The method was found to be suitable for rapid determination of enantiomeric purity of bicalutamide in bulk drugs and pharmaceutical formulations.     

Congenital pseudarthrosis of the ulna

We report a case of congenital pseudarthrosis of the ulna along with generalized neurofibromatosis (type I). The patient had a good clinical outcome after single-bone forearm reconstruction. In the setting of radial head dislocation following long-standing congenital pseudarthrosis of the ulna, single-bone forearm reconstruction is a viable option. It prevents the loss of hand function by the effective shortening of flexor tendons and spares movements of the humeroulnar and radiocarpal joints.     

Differential involvement of enkephalins in analgesic tolerance, locomotor sensitization, and conditioned place preference induced by morphine

In this study, the authors investigated the role of enkephalins in morphine-induced conditioned place preference, locomotor sensitization, and analgesic tolerance. Both preproenkephalin wild type (ppENK [+/+]) and knockout (ppENK [-/-]) mice showed similar preference for the morphine-paired chamber over the vehicle-paired chamber, indicating morphine induced comparable conditioned place preference in ppENK (+/+) and ppENK (-/-) mice. Sensitization developed to the motor stimulatory action of morphine after its repeated administration, but the magnitude of this response was not altered in ppENK (-/-) mice. However, as shown previously, ppENK (-/-) mice displayed blunted morphine analgesic tolerance. Taken together, the results suggest that enkephalins may be important for the development of analgesic tolerance but not for conditioned place preference or behavioral sensitization induced by morphine.     

IL-10 high producing genotype predisposes HIV infected individuals to TB infection

Interleukin (IL-10), an anti-inflammatory cytokine, is known to have dual effect on the host immune system. One of these roles is that it provides an effective autoregulatory mechanism which protects the host from excessive inflammation and tissue damage which is in part initiated by the Th1 driven pro-inflammatory immune responses during infections (such as TB, HIV and malaria). However, though beneficial, this autoregulatory mechanism is at times exploited by pathogens which evade elimination by Th1 driven immune response leading to chronic infections. The main aim of this study therefore was to study the influence of IL-10 polymorphism in relation to its levels with respect to HIV-TB co-infection. A total of 452 participants were categorized into HIV (121), active tuberculosis (TB) (118), HIV-TB (HT) (106) groups and healthy control group (107). Polymorphism for IL-10 gene (positions -1082, -819, -592) was studied using ARMS-PCR, RFLP. IL-10 and IFN-γ levels in antigen stimulated cultures were measured using ELISA. Statistical analysis was performed using Chi-Square (χ(2)) test, One-way ANOVA and t-tests. IL-10 (-1082) GG genotype was positively associated with HIV-TB, whereas AG with HIV and AA with TB. The cohort with GG genotype also had significantly high stimulated levels of IL-10 compared to AG and AA. AC genotype was significantly frequent in HIV-TB group at IL-10 (-592) position when compared with controls. HIV positive individuals with GG genotype at IL-10 (-1082) position and high IL-10 levels may have a high risk of developing TB co-infection.     

An update on the contribution of hot-melt extrusion technology to novel drug delivery in the twenty-first century: part I

Introduction: Currently, hot melt extrusion (HME) is a promising technology in the pharmaceutical industry, as evidenced by its application to manufacture various FDA-approved commercial products in the market. HME is extensively researched for enhancing the solubility and bioavailability of poor water-soluble drugs, taste masking, and modifying release in drug delivery systems. Additionally, its other novel opportunities or pharmaceutical applications, and capability for continuous manufacturing are being investigated. This efficient, industrially scalable, solvent-free, continuous process can be easily automated and coupled with other novel platforms for continuous manufacturing of pharmaceutical products.

Areas covered: This review focuses on updates on solubility enhancement of poorly water-soluble drugs and process analytical tools such as UV/visible spectrophotometry; near-infrared spectroscopy; Raman spectroscopy; and rheometry for continuous manufacturing, with a special emphasis on fused deposition modeling 3D printing.

Expert opinion: The strengths, weakness, opportunities, threats (SWOT) and availability of commercial products confirmed wide HME applicability in pharmaceutical research. Increased interest in continuous manufacturing processes makes HME a promising strategy for this application. However, there is a need for extensive research using process analytical tools to establish HME as a dependable continuous manufacturing process.