Osteoporosis: Investigations and Monitoring.

Background: Osteoporosis is characterized by microarchitectural disruption of the bone, decrease in bone mineral density, and increased skeletal fragility and risk of fracture. Osteoporosis occurs due to the decoupling of bone formation and bone resorption, with a significant increase in resorption. This review article focuses on the role of laboratory investigations in the diagnosis and monitoring of treatment in patients with osteoporosis.

Diagnostic and Therapeutic Challenges in Ocular Histoplasmosis - A Case Report.

To report a rare case of skin biopsy proven Histoplasma panuveitis. Observational case report of a 76-year-old Asian Indian man presented as panuveitis. Clinical course, diagnostic and treatment difficulties and confocal microscopy findings were studied.

Alteration of skin hydration and its barrier function by vehicle and permeation enhancers: a study using TGA, FTIR, TEWL and drug permeation as markers.

Vehicles and permeation enhancers (PEs) used in transdermal drug delivery (TDD) of a drug can affect skin hydration, integrity and permeation of the solute administered. This investigation was designed to study the effect of the most commonly used vehicles and PEs on rat skin hydration, barrier function and permeation of an amphiphilic drug, imipramine hydrochloride (IMH). An array of well-established techniques were used to confirm the findings of the study.

Solid-state characterization of nevirapine.

The purpose of this investigation is to characterize nevirapine from commercial samples and samples crystallized from different solvents under various conditions. The solid-state behavior of nevirapine samples was investigated using a variety of complementary techniques such as microscopy (optical, polarized, hot stage microscopy), differential scanning calorimeter, thermogravimetric analysis, Fourier transform infrared spectroscopy and powder X-ray diffractometry. The commercial samples of nevirapine had the same polymorphic crystalline form with an anhedral crystal habit.

Thermoreversible liposomal poloxamer gel for the delivery of paclitaxel: dose proportionality and hematological toxicity studies.

The currently existing treatment modalities of cancer suffer from a major drawback of systemic toxicity, which results from high systemic drug exposure. Delivery of chemotherapeutic agents by delivery systems that alleviate systemic side effects but at the same time provide therapeutic advantage by controlling tumor growth exists as a viable option. To achieve this objective, a thermo reversible poloxamer gel containing paclitaxel incorporated in liposomes was formulated at three dose loadings.

Effect of amorphous content on dissolution characteristics of rifampicin.

Rifampicin, one of the main first line anti-TB drugs, shows variable bioavailability in different marketed preparations and reasons cited include physiological, degradation, manufacturing/ processing, solid state, and bioavailability assessment procedure. Although the amorphous form of a drug is expected to exhibit higher solubility, the amorphous rifampicin has been reported to have a solubility disadvantage as compared to crystalline form II, which is used in marketed preparations. Amorphous form was generated and characterized by solid-state characterization techniques.

Fluorescence anisotropy, FT-IR spectroscopy and 31-P NMR studies on the interaction of paclitaxel with lipid bilayers.

To understand the bilayer interaction with paclitaxel, fluorescence polarization, Fourier transform infrared spectroscopy (FT-IR) and 31-phosphorus nuclear magnetic resonance (31P-NMR) studies were performed on paclitaxel bearing liposomes. Fluorescence anisotropy of three probes namely, 1,6-diphenyl-1,3,5-hexatriene (DPH), 12-(9-anthroyloxy) stearic acid (12AS) and 8-anilino-1-naphthalene sulfonate (ANS) were monitored as a function of paclitaxel concentration in the unsaturated bilayers. The incorporation of paclitaxel decreased anisotropy of 12AS and ANS probes, while slightly increased anisotropy of DPH.

Dermal drug delivery: Revisited.

The unique histological and molecular organization of skin poses a formidable barrier to drug delivery into and across skin. Due to the severe restrictions on molecular transport, only potent and lipophilic drug candidates have been able to successfully enter the market. New drug discovery programs based on high-throughput screening and combinatorial chemistry have lead to synthesis of potent but highly lipophilic molecules, and yet these molecules are difficult to deliver by conventional routes of administration.

A decision tree for rapid quality assurance and control of rifampicin-containing oral dosage forms for global distribution for tuberculosis treatment.

For centuries tuberculosis remained as a complex socioeconomic problem impeding human development. Directly observed treatment short-course and fixed dose combinations were implemented in tuberculosis therapy for maximum success of treatment. However, drug shortages primarily hindered the expansion of directly observed treatment short-course, which lead to development of the global tuberculosis drug facility.

Studies of the skin permeation of lipophilic drugs: paclitaxel.

The objective of this investigation was to develop and validate skin permeation methodology for a highly lipophilic drug with respect to sink conditions and intactness of barrier during the course of experiment, using water permeation and trans epidermal water loss as tools.

Stability of insulin under iontophoretic conditions.

The present study focuses on the physical and chemical stability of insulin under iontophoretic conditions using HPLC, SDS-PAGE, RIA and biological assay. Influence of pH, concentration of insulin, current strength and duration of current application on the stability of insulin was studied. Anodal iontophoresis at pH 7.

Dissolution testing of marketed rifampicin containing fixed dose combination formulations using a new discriminative media: a post marketing retrospective study.

Currently recommended compendial dissolution methods for quality control of orally administered solid dosage forms of rifampicin containing formulations are not found to be able to forecast the in vivo performance. A recently proposed dissolution method of 0.01 N HCl at 50 rpm using paddle apparatus for screening was found to be more appropriate and able to predict the in vivo performance of those formulations.

Role of anticyclic citrullinated peptide in the diagnosis of early rheumatoid factor-negative suspected rheumatoid arthritis: is it worthwhile to order the test?

Background: Anticyclic citrullinated peptide (anti-CCP) is a relatively new serologic marker, which has been proposed for use in the diagnosis of rheumatoid arthritis (RA) and is said to be a highly specific.

Objective: The aim of the study was to evaluate the role of anti-CCP in a South Indian population of patients with suspected RA in the early stages when rheumatoid factor is negative and clinical presentation is atypical.

Methods: Patients with early inflammatory arthritis who were rheumatoid factor-negative were investigated for anti-CCP.

High-throughput evaluation of non-swellable controlled release matrix tablets.

Drug release from controlled-release (CR) matrix tablets involves the permeation and diffusion of water through the system. In this study, a new methodology is proposed for the measurement of water permeation and simultaneous drug release from the inert, non-swellable CR matrix tablet of diltiazem (DLT) and a correlation is made between these two processes. Cylindrical matrices were readily prepared by direct compression of pellets obtained by extrusion-spheronization.

Nanoemulsions as versatile formulations for paclitaxel delivery: peroral and dermal delivery studies in rats.

Pathogenesis of psoriasis involves the keratinocytes in epidermis as well as the angiogenesis involving deeper skin layers. So, the drug delivery strategy should be customized to localize paclitaxel (PCL) inside both layers. In this investigation, in order to achieve penetration of PCL into deeper skin layers while minimizing the systemic escape, a nanoemulsion (NE) was formulated and evaluated its in vivo pharmacokinetic performance.

An ex vivo characterization of Paclitaxel loaded chitosan films after implantation in mice.

The objective of present investigation was the characterization of chitosan films after in vivo implantation. Chitosan films were prepared at three dose loadings of paclitaxel by classical casting method. They were implanted subcutaneously in Swiss mice in the neck region and were removed at 7, 15, 21 and 30 days post implantation for characterization.

Functional role of P-glycoprotein in limiting peroral drug absorption: optimizing drug delivery.

P-glycoprotein (P-gp) associated multi-drug resistance is one of the major challenges in the chemotherapy of various cancers. On the other hand, it is now widely recognized that P-gp influences drug transport across various biological membranes. To this end, there is an increasing trend to optimize pharmacokinetics and drug delivery right from the initial stages of drug discovery by exploring all the possible mechanisms involved in 'deliverability'.

Plasma pooling to expedite bioequivalence estimation of rifampicin in fixed dose combinations.

Rifampicin has been found to be one of the most important antitubercular drugs; however, variable bioavailability of rifampicin in some fixed dose combinations (FDCs) as well as separate formulations has been reported in the literature. This resulted in proper evaluation of FDCs with standard protocol for bioequivalence trials. Earlier, plasma pooling as a rapid method for bioequivalence assessment of rifampicin in FDCs was proposed from our laboratory.

Statistical evaluation of physiological variability of rifampicin in fixed dose combinations.

Tuberculosis is one of the microbial diseases having a long history of its occurrence and yet to be eradicated from the world. Due to the development of bacterial resistance, treatment has changed from monotherapy to combotherapy to fixed dose combinations (FDCs). Rifampicin has been found one of the most important anti-tubercular drugs, however variable bioavailability of rifampicin in some FDCs as well as separate formulations has been reported in the literature, and led to the development of WHO model protocol for evaluation of FDCs for bioequivalence trials.

Simultaneous determination of lamivudine and stavudine in antiretroviral fixed dose combinations by first derivative spectrophotometry and high performance liquid chromatography.

Two methods are described for the simultaneous determination of lamivudine (3TC) and stavudine (d4T) in combined pharmaceutical tablets. The first method depends on first derivative UV-spectrophotometry with zero-crossing measurement technique. The first derivative absorbances at 280 and 300 nm were selected for the determination of stavudine and lamivudine, respectively.

Co-treatment with grapefruit juice inhibits while chronic administration activates intestinal P-glycoprotein-mediated drug efflux.

P-Glycoprotein (P-gp) mediated efflux is recognized as a significant biochemical barrier affecting oral absorption for a number of drugs. Various conflicting reports have been published regarding the effects of grapefruit juice (GFJ) on P-gp-mediated drug efflux, in which GFJ has been shown both to inhibit and activate it. Hence, the present study adopted a two-way approach, involving both co-treatment and chronic administration.

Minimum sample size and sampling time requirements for assessment of rifampicin bioequivalence from FDC formulations.

Setting: The WHO- and IUATLD-recommended protocol for rifampicin (RMP) bioequivalence utilises 20-22 volunteers and 8 h, whereas the requirement of other regulatory authorities is 12 volunteers with a 24 h sampling schedule. Differing sampling size and time requirements may change the outcome of RMP bioequivalence.

Objective: To determine the minimal sample size and time required to assess RMP bioequivalence from FDC formulations.

Quality control of anti-tuberculosis FDC formulations in the global market: part II-accelerated stability studies.

Objective: To determine the quality and performance of rifampicin (RMP) containing fixed-dose combination (FDC) formulations of anti-tuberculosis drugs sourced from the international market with respect to physical, chemical and dissolution properties after storage at accelerated stability conditions (40 degrees C/75% relative humidity) and to identify appropriate storage specifications.

Methods: Formulations across different companies and combinations were subjected to 6-month accelerated stability testing in packaging conditions recommended by the manufacturer. Various pharmacopeial and nonpharmacopeial tests for tablets were performed for 3- and 6-month samples.