T. M. Pramod Kumar

Development of a Novel Biodegradable Superporous Hydrogel for Gastroretentive Application

The objective of the study was to design and evaluate a novel superporous hydrogels (SPHs) for application as gastroretentive dosage form of losartan potassium. The semi-interpenetrating polymer network (IPN) SPHs of polyvinyl pyrrolidone and chitosan was synthesized by crosslinking chitosan with glyoxal. SEM photographs show the presence of interconnected pores. The prepared SPHs were highly sensitive to pH of swelling media, and showed reversible swelling and deswelling behaviors maintaining their mechanical stability. Drug release fitted best to the Korsmeyer-Peppas model. The studies showed that semi-IPN SPHs could be used as a gastroretentive drug delivery system.

Methotrexate: A Gold Standard for Treatment of Rheumatoid Arthritis

ABSTRACT Rheumatoid arthritis (RA) is a painful, debilitating disease characterized by inflammation of the joints, with the proliferation of the synovium and the progressive erosion of cartilage and bone. The treatment of RA is still unsatisfactory, but a number of powerful disease-modifying antirheumatic drugs have become available, such as methotrexate (MTX). Even in the current era of biological targeted therapies, MTX remains the initial preferred antirheumatic drug and is considered to be the gold standard for treatment of RA. The combination of its perceived efficacy, acceptable safety profile, and low cost, as well as decades of clinical experience, makes MTX the cornerstone of treatment for RA and the anchor drug in combination with various biological agents. In this review, the authors aim to summarize the research done in the field of drug delivery systems of MTX according to its routes of administration for treatment of RA. The last part of the review addresses combination therapy with MTX and future direction in the drug delivery of MTX. This review also provides the reader with a general overview of RA and its therapeutic strategies with respect of MTX, which may bring uniformity in medical practice for effective management of RA.

Intra-articular delivery of a methotrexate loaded nanostructured lipid carrier based smart gel for effective treatment of rheumatic diseases

A nanostructured lipid carrier (NLC) based smart gel of methotrexate (MTX) was developed as a potential system for the treatment of rheumatic diseases (RD). NLC composed of Compritol ATO 888 as the solid lipid, Capmul MCM EP as the liquid lipid, Tween 80 as the surfactant and PEG 400 as the co-surfactant was prepared by modified hot homogenization followed by melt ultrasonication. The prepared NLC dispersion was characterized for particle size, polydispersity index (PDI), entrapment efficiency and zeta potential. The nanoparticulate dispersion was suitably gelled into the polymer matrices of Pluronic F-127 (PF-127) and Pluronic F-68 (PF-68). Two-factor three-level full factorial design was employed to determine the optimum concentrations of PF-127 and PF-68. The prepared NLC based smart gel was evaluated for viscosity, sterility, thermosensitivity, syringeability, content uniformity and in vitro release behaviour. The efficacy and biocompatibility of the NLC based smart gels were established using an adjuvant arthritis model and histology analysis, respectively. The NLCs had an average particle size of 107 ± 6 nm with a PDI of 0.365 ± 0.03, entrapment efficiency of 69.53% ± 1.23% and zeta potential of −13.54 ± 1.1 mV. The optimized NLC based smart gel (F-10) was found to be thermo-sensitive and exhibited 92.41% drug release at 108 h. The results demonstrated that MTX was evenly distributed in the optimized formulation, which was sterile and syringeable through an 18 gauze needle. A significant decrease in rat joint swelling was observed using the MTX-NLC based gel during a 28 day period. In conclusion, this MTX-NLC based gel could be a potential formulation for intra-articular treatment of inflammation in rheumatic conditions.

Development, in vitro and in vivo Evaluation of Novel Injectable Smart Gels of Azithromycin for Chronic Periodontitis

Periodontitis is an inflammatory condition affecting teeth resulting in progressive destruction of periodontal ligaments, resorption of alveolar bone and loss of teeth. Treatment of periodontitis includes surgical and non surgical management. Systemic antibiotics are also used for the treatment of periodontitis. The aim of this research was to formulate smart gel system of azithromycin (AZT) and to evaluate in vitro and in vivo for non-surgical treatment of chronic periodontitis. Azithromycin dihydrate, used systemically in the treatment of periodontitis, was formulated into smart gels using biodegradable, thermosensitive polymer Pluronic® F-127 (PF-127) and Hydroxy Ethyl Cellulose (HEC) as copolymer. The prepared smart gels were evaluated for sterility, content uniformity, gelation temperature and time, syringeability, rheological behavior, in vitro diffusion and in vivo efficacy in human patients. The prepared smart gels were clear and transparent, sterile, thermoresponsive and injectable. Viscosity of gels increased with increase in concentration of polymer/co-polymer and also with temperature. They gelled in short response time below the body temperature. In vitro release studies showed controlled drug release which was influenced significantly by the properties and concentration of PF-127 and HEC. In vivo efficacy studies showed a significant improvement (p <0.001) in clinical parameters such as gingival index, probing pocket depth, clinical attachment level, bleeding index and plaque index. The developed azithromycin smart gel system is a novel approach for the treatment of chronic periodontitis since it reduces the dose and side effects, bypasses the usual surgical procedures and improves patient compliance.

Regulations of Medical Devices in Regulated Countries A Comparative Review

The term “medical device” covers a vast range of equipment, from simple tongue depressors to hemodialysis machines. Like medicines and other health technologies, they are essential for patient care. With the increased use of medical devices, stringent regulatory standards are required to ensure that the devices are well studied, safe, and well tolerated. Recently, introduced guidelines and amendments in the laws of the US, Europe, and Canada provide adequate guidance for both manufacturers and competent authorities to prevent defects and performance failures efficiently and appropriately. A defective device may result in inaccurate patient results, leading to misdiagnosis, delays in treatment, adverse events, injuries, or even death. Therefore, a thorough review of the medical device before being released for use by the public and effective monitoring of the medical device once placed on the market are crucial.

Formulation and Evaluation of Non-Effervescent Floating Tablets of Losartan Potassium

The aim of the work is to modify the solubility and bioavailability of Losartan potassium, by employing noneffervescent floating drug delivery (tablet dosage forms). Non-effervescent systems are a type of floating drug delivery systems, that have been used to boost the gastric residence and the floatation time in the gastro intestinal tract. The study included formulation of floating tablets using polymers like Chitosan and Karaya gum as matrix forming agents. Accurel(®) MP 1000 was used as floating agent. The tablets were prepared by direct compression technique. FTIR, DSC studies conformed that there was no incompatibility between the polymer and the drug. Tablet preformulation parameters were within the Pharmacopoeial limit. Tablet showed zero lag time, contisnuance of buoyancy for >12 h. The tablet showed good in vitro release. Drug release was through swelling and abided by the gellation mechanism. In vivo X-ray studies depicted that tablets continued to float in the GIT for 12 h. Accelerated stability showed that, tablets were stable for over 6 month. Thus the prepared non-effervescent floating tablet of Losartan potassium can be used for the treatment of hypertension for more than 12 h with single dose administration.

pH-0064ependent gradient release microspheres of lercanidipine hydrochloride: in vitro and in vivo evaluation

Poorly water-soluble drugs pose the problem of low availability due to their limited solubility in the varying pH of the gastrointestinal tract (GIT). The aim of the present study was to develop a pH-dependent gradient-release drug delivery system for a poorly water-soluble drug, Lercanidipine HCl, a dihydropyridine calcium channel antagonist, wherein the drug is released all along the GIT. Microspheres were prepared by quasi-emulsion solvent diffusion method. In this method solid drug was dispersed as a matrix structure using three types of pH-dependent polymers viz., Eudragit E100 (for pH 1.2), Hydroxyl propyl methyl cellulose phthalate (for pH ≥ 5.5) and Eudragit S100 (for pH ≥ 7) in different weight ratios. pH-dependent microspheres were characterized in terms of their shape, size, production yield, drug loading and entrapment efficiency. The in vitro drug release was performed at different pH conditions. The bioavailability studies were carried out in rabbits. pH-dependent microspheres were spherical in shape and were in the size range of 288-394 μm. X-ray diffraction studies confirmed the molecular dispersion of the drug in amorphous state. The results showed that the release rate of drug from microspheres was influenced by varying the type and concentration of pH-dependent polymers employed. The drug was released only in particular pH based on the polymer used. The in vitro release followed Fickian diffusion mechanism. The results of the bioavailability testing in rabbits suggested that the pH-dependent delivery system could improve efficiently the uptake of the poorly water-soluble drug and prolong the Tmax value in vivo. These findings suggested that a microsphere-based pH-dependent drug delivery system may be prepared for the delivery of Lercanidipine HCl for improving its bioavailability.

Use of computerized systems in clinical research: A regulatory perspective

Electronic source data and documentation from clinical investigations should be attributable, legible, contemporaneous, original and accurate. 21 Code of Federal Regulations (CFR) Part 11 provides acceptance criteria for electronic records, signatures, and handwritten signatures executed to electronic records. All study protocols should identify each step at which a computerized system will be used to create, modify, maintain, archive, retrieve, or transmit source data. Standard operating procedures and controls should be established when using computerized systems to create, modify, maintain, or transmit electronic records, and when collecting source data at clinical trial sites. Access must be limited to authorized individuals. Computer generated, time-stamped electronic audits trails should be undertaken to track changes to electronic source documentation. Controls should be established to ensure that the system’s date and time are correct. Procedures and controls should be put in place to prevent the altering, browsing, querying, or reporting of data via external software applications that do not enter through the protective system software. Prompts, flags, or other help features should be incorporated in a computerized system to encourage consistent use of clinical terminology. Individuals should have training necessary to perform their assigned tasks.