H. G. Shivakumar

Solubility enhancement and delivery systems of curcumin a herbal medicine: a review.

Curcumin diferuloylmethane is a main yellow bioactive component of turmeric, possess wide spectrum of biological actions. It was found to have anti-inflammatory, antioxidant, anticarcinogenic, antimutagenic, anticoagulant, antifertility, antidiabetic, antibacterial, antifungal, antiprotozoal, antiviral, antifibrotic, antivenom, antiulcer, hypotensive and hypocholesteremic activities. However, the benefits are curtailed by its extremely poor aqueous solubility, which subsequently limits the bioavailability and therapeutic effects of curcumin. Nanotechnology is the available approach in solving these issues. Therapeutic efficacy of curcumin can be utilized effectively by doing improvement in formulation properties or delivery systems. Numerous attempts have been made to design a delivery system of curcumin. Currently, nanosuspensions, micelles, nanoparticles, nano-emulsions, etc. are used to improve the in vitro dissolution velocity and in vivo efficiency of curcumin. This review focuses on the methods to increase solubility of curcumin and various nanotechnologies based delivery systems and other delivery systems of curcumin.

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.

Polyacrylamide grafted guar gum based glimepiride loaded pH sensitive pellets for colon specific drug delivery: fabrication and characterization

Purpose: The purpose of this study was to prepare pH-sensitive pellets using an extrusion-spheronization pelletization (ESP) technique. Method: Polyacrylamide-grafted-guar gum (pAAm-g-GG) was prepared by taking three different ratios of guar gum to acrylamide (1 : 2, 1 : 3.5 and 1 : 5). Amide groups of these grafted copolymers were converted into carboxylic functional groups. Fourier transform infrared (FT-IR) spectroscopy, Differential Scanning Calorimetry (DSC) and 1H-NMR spectroscopy were used to characterize the grafted copolymers. Pellets were prepared by pAAm-g-GG (1.0–4.5%) and microcrystalline cellulose incorporating an anti-diabetic drug viz., glimepiride. Here, variables were studied and pellets were characterized for average size, surface morphology, friability, bulk density and flow properties. In vitro drug release was carried out in simulated gastric and intestinal conditions. Result: The in vitro drug release profile indicated an increase in drug release retardation with increasing pAAm-g-GG concentration. The formulated pellets were stable with respect to their physicochemical characters and drug content over a period of 60 days at different temperatures and relative humidity. Conclusion: It has been concluded that the prepared pellets demonstrate the potential use of MCC and pAAm-g-GG for the development of pH sensitive colon specific controlled drug delivery systems of glimepiride for diabetic therapy.

Feasibility of polyvinyl alcohol as a transdermal drug delivery system for terbutaline sulphate

A series of terbutaline sulphate drug incorporated polyvinyl alcohol (PVA) matrix films were produced by the solvent evaporation method. The effect of xanthan gum and plasticizers (propylene glycol and dibutyl phthalate) on the rate and amount of drug diffusion from PVA membrane across the hydrated cellophane membrane has been evaluated, using an open glass diffusion‐tube. The obtained films were clear, smooth and flexible having sufficient mechanical strength. The mechanical performance of the dry PVA films with xanthan gum and plasticizers were also ascertained. Polyvinyl alcohol‐xanthan gum blends showed a high rate of drug release compared to that of polyvinyl alcohol film alone. Among the two plasticizers employed, propylene glycol showed better permeability. Among different formulations studied, the formulation PVA/xanthan gum/propylene glycol (F7) was found to be an optimized composition for efficient transdermal delivery of the model drug, terbutaline sulphate. The mechanism of drug diffusion has been evaluated using the Peppas model. Stability studies carried out on polymer‐drug formulations revealed that the drug is stable at 40°C and 75% RH for a period of 6 weeks.

Design and optimization of clotrimazole–hydroxypropyl-β-cyclodextrin bioadhesive vaginal tablets using Anacardium occidentale gum by 32 factorial design

Clotrimazole (CTZ), a BCS class II drug, is widely employed in the treatment of vaginal candidiasis. However, due to its poor solubility, repeated administrations are required to maintain a therapeutic concentration. To increase its aqueous solubility, it was complexed with hydroxypropyl-β-cyclodextrin (HPβCD) and formulated as vaginal tablets using natural Anacardium occidentale gum in combination with Carbopol 934P. The formation of a drug–HPβCD complex was confirmed by characterization techniques, viz., scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), 1H NMR and Fourier transform infrared spectroscopy (FT-IR) studies. Furthermore, 32 factorial design was employed to optimize the gum and Carbopol 934P concentrations in the development of CTZ–HPβCD vaginal tablets. In vitro analysis revealed the higher susceptibility of Candida albicans strains and significant mucoadhesion of the tablet formulation. Based on our findings, combined with Anacardium occidentale gum, the CTZ–HPβCD complex could be used for treating fungal infections, and it offers the great advantage of the higher solubility of CTZ with the therapeutic importance of higher bioavailability at the site of action. In addition, the use of natural polymers could also serve to minimize drug toxicity, which would be particularly useful for treating vaginal candidiasis safely in pregnancy.

Current Perspectives on Novel Drug Delivery Systems and Approaches for Management of Cervical Cancer: A Comprehensive Review

Cervical cancer is uterine cervix carcinoma, the second deadly cancer and has a high incidence and mortality rate. In the developing world conventional treatment strategies such as surgical intervention and chemoradiotherapy are less widely available. Currently cancer research focuses on improving treatment of cervical cancer using various therapies such as gene therapy, recombinant protein therapy, photodynamic therapy, photothermal therapy and delivery of chemotherapeutic agents using nanoparticles, hydrogel and liposomal based delivery systems and also localized delivery systems which exist in a variety of forms such as intravaginal rings, intravaginal patches, intravaginal films, etc. in order to improve the drug delivery in a controlled manner to the diseased site thereby reducing systemic side effects. The present review encloses existing diverse delivery systems and approaches intended for treatment of cervical cancer.

Porous nanoparticles of metoprolol tartrate produced by spray-drying: development, characterization and in vitro evaluation.

The present investigation was undertaken to fabricate porous nanoparticles of metoprolol tartrate by spray-drying using ammonium carbonate as pore former. Prepared nanoparticles were coated with Eudragit S100 polymer in order to prevent the release of metoprolol tartrate in the upper GI tract. It was shown that nanoparticles with low size ranges can be obtained with a low feed inlet rate. Micromeritic studies confirmed that nanoparticle batches are discrete and free flowing. Effects of the pore former on drug loading, porosity and in vitro release were studied. It was found that there was an increase in drug loading and porosity with increasing the amount of pore former. In vitro drug release studies showed that an increase in pore former made drug release faster. Release kinetics proved that nanoparticles follow a zero-order release mechanism. U radu je opisana priprava poroznih nano~estica metoprolol tartarata pomo}u su{enja sprejanjem, koriste}i amonijev karbonat za stvaranje pora. Da bi se sprije~ilo osloba- |anje metoprolol tartarata u gornjem dijelu GI trakta, nano~estice su oblo`ene polimerom Eudragit S100. Nano~estice podjednake veli~ine mogu se dobiti polaganim uklapanjem ljekovite tvari. Mikromeri~ke studije potvrdile su da su nano~estice zasebne i te~ne. Prou- ~avan je utjecaj sredstva za stvaranje pora na koli~inu uklopljenog lijeka, poroznost i invitro osloba|anje. Pove}anje koli~ine sredstva za stvaranje pora pove}ava koli~inu uklopljenog lijeka, poroznost i brzinu osloba|anja ljekovite tvari. Osloba|anje metoprolola slijedi kinetiku nultog reda

Design and development of a dual-drug loaded pulsatile capsule for treatment of hypertension – in vitro and ex vivo studies

The frequency of incidence of cardiovascular events in hypertensive patients is higher in the early morning hours between 5 a.m. to noon due to a sharp increase in blood pressure (BP), thereby suggesting a circadian pattern. Currently available antihypertensive medicines for bed time or morning dosing cannot address this early morning surge in BP. The aim of the present study was to design and evaluate a pulsatile dosage form to program the release of dual antihypertensive drugs to mimic the circadian pattern of BP. The optimized formulation meant for bedtime dosing, consisted of an insoluble capsule body housing a layer of swellable polymer, a telmisartan (TELMI) tablet sealed by an erodible polymer tablet. The capsule body was closed with a water soluble cap containing fast releasing amlodipine (AMLO)–xylitol granules. The developed formulation was studied for physical characteristics, lag time determination, in vitro release, and ex vivo dissolution absorption. The capsule cap dissolved in acidic pH to release 98.67% of the AMLO within 3 h. The swellable polymer layer at the base of capsule pushed the plug along with the TELMI tablet out after a lag time of 6–7 h with 77.97% drug being released at the end of 12 h providing a time controlled need based release. In vitro–ex vivo studies revealed a better degree of correlation in the pulsatile capsule compared to the marketed one. Thus this approach can be useful for the timed release of a combination antihypertensive medication and may provide effective 24 h control of BP in hypertensive patients.