Meka Venkata Srikanth

Chronotherapeutic Drug Delivery Systems - An Approach to Circadian Rhythms Diseases

The purpose of writing this review on chronotherapeutic drug delivery systems (ChrDDs) is to review the literatures with special focus on ChrDDs and the various dosage forms, techniques that are used to target the circadian rhythms (CR) of various diseases. Many functions of the human body vary considerably in a day. ChrDDs refers to a treatment method in which in vivo drug availability is timed to match circadian rhythms of disease in order to optimize therapeutic outcomes and minimize side effects. Several techniques have been developed but not many dosage forms for all the diseases are available in the market. ChrDDs are gaining importance in the field of pharmaceutical technology as these systems reduce dosing frequency, toxicity and deliver the drug that matches the CR of that particular disease when the symptoms are maximum to worse. Finally, the ultimate benefit goes to the patient due the compliance and convenience of the dosage form. Some diseases that follow circadian rhythms include cardiovascular diseases, asthma, arthritis, ulcers, diabetes etc. ChrDDs in the market were also discussed and the current technologies used to formulate were also stated. These technologies include Contin® , Chronotopic®, Pulsincaps®, Ceform®, Timerx®, Oros®, Codas®, Diffucaps®, Egalet®, Tablet in capsule device, Core-in-cup tablet technology. A coated drug-core tablet matrix, A bi-layered tablet, Multiparticulate-based chronotherapeutic drug delivery systems, Chronoset and Controlled release microchips.

Investigation on in vitro dissolution rate enhancement of indomethacin by using a novel carrier sucrose fatty acid ester

Background and the purpose of the studyThe purpose of the present investigation was to characterize and evaluate solid dispersions (SD) of indomethacin by using a novel carrier sucrose fatty acid ester (SFE 1815) to increase its in vitro drug release and further formulating as a tablet.MethodsIndomethacin loaded SD were prepared by solvent evaporation and melt granulation technique using SFE 1815 as carrier in 1:0.25, 1:0.5 1:0.75 and 1:1 ratios of drug and carrier. Prepared SD and tablets were subjected to in vitro dissolution studies in 900 mL of pH 7.2 phosphate buffer using apparatus I at 100 rpm. The promising SD were further formulated as tablets using suitable diluent (DCL 21, Avicel PH 102 and pregelatinised starch) to attain the drug release similar to that of SD.. The obtained dissolution data was subjected to kinetic study by fitting the data into various model independent models like zero order, first order, Higuchi, Hixon-Crowell and Peppas equations. Drug and excipient compatibility studies were confirmed by fourier transform infrared spectroscopy, X-ray diffraction, differential scanning calorimetry and scanning electron microscopy.ResultsThe in vitro dissolution data exhibited superior release from formulation S6 with 1:0.5 drug and carrier ratio using solvent evaporation technique than other SDs prepared at different ratio using solvent evaporation and melt granulation technique. The in vitro drug release was also superior to that of the physical mixtures prepared at same ratio and also superior to SD prepared using common carriers like polyvinyl pyrollidone and PEG 4000 by solvent evaporation technique. Tablets (T8) prepared with DCL21 as diluent exhibited superior release than the other tablets. The tablet formulation (T8) followed first order release with Non-Fickian release.ConclusionSFE 1815 a novel third generation carrier can be used for the preparation of SD for the enhancement of in vitro drug release of indomethacin an insoluble drug belonging to BCS class II.

Chronotherapeutic Drug Delivery from Indomethacin Compression Coated Tablets for Early Morning Pain Associated Rheumatoid Arthritis

As the main intent of delivering maximum concentration of drug available from the dosage form, an oral compression coated tablet (CCT) was intended to develop with a predetermined lag time of 6 hrs before immediate release of drug to target circadian rhythms of rheumatoid arthritis. Solid dispersions are promising approach to enhance drug release, which later will be developed as core tablet formulation and compression coated with polyethylene oxide (PEO WSR 303). Solid dispersions were formulated with different ratio of drug and carrier (sucrose fatty acid esters 1811) using solvent evaporation and melt granulation technique, optimized solid dispersion was formulated as core tablet with different diluents. Optimized core tablet was compression coated with PEO WSR 303 along with a channeling agent (DCL 21, mannitol, HPMC 5 cps and starch 1500). Lag time before immediate release of drug was markedly dependent on weight ratios of polymer and channeling agent used, which ranged from 4 to 12 hrs. Optimized solid dispersion (S9) was used for formulating optimized core tablet formulation (C8). CCT (T8) prepared with core tablet (C8) along with mannitol provided a lag time of 6 hrs with minimum concentration of channeling agent used, which was also supported from the permeability study results. Incompatibility and characterization was confirmed from DSC, XRD, FTIR and SEM studies. Unaltered Cmax and AUC0-t but delayed Tmax following oral ingestion of optimized formulation (T8) to human volunteers indicated clear lag time before immediate release of drug, which is suitable for treating rheumatoid arthritis following circadian rhythm.

Design and evaluation of lornoxicam bilayered tablets for biphasic release

The objective of the present investigation was to develop bilayered tablets of lornoxicam to achieve biphasic release pattern. A bilayered tablet, consisting of an immediate and controlled release layer, was prepared by direct compression technique. The controlled release effect was achieved by using various hydrophilic natural, semi synthetic and synthetic controlled release polymers such as xanthan gum, hydroxypropyl methylcellulose (HPMC) and polyethylene oxide (PEO) to modulate the release of the drug. The in vitro drug release profiles showed the biphasic release behavior in which the immediate release (IR) layer containing the lornoxicam was released within 15 minutes, whereas the controlled release (CR) layer controlled the drug release for up to 24 h. All the bilayered tablets formulated have followed the zero order release with non-Fickian diffusion controlled release mechanism after the initial burst release. FTIR studies revealed that there was no interaction between the drug and polymers used in the study. Statistical analysis (ANOVA) showed no significant difference in the cumulative amount of drug release after 15 min, but significant difference (p < 0.05) in the amount of drug released after 24 h from optimized formulations was observed. Based on the release kinetic parameters obtained, it can be concluded that xanthan gum polymer was suitable for providing a biphasic release of lornoxicam.

Formulation and Evaluation of Gastro Retentive Floating Drug Delivery System for Propranolol HCl

Asiaticoside is a triterpene obtained from Centella asiatica and demonstrated to have healing potential against various wound models. Wounds are inflicted for constructive reasons even though more often they are results of accidents. This work aims at identifying molecular targets which account for the therapeutic results attributed to the use of asiaticoside. Even though exact mechanisms of action have not been reported, experimental evidences point at the inhibition of pro-inflammation and enhanced tissue regeneration. Keywords: asiaticoside, Centella asiatica , wounds, wound healing

Development and evaluation of a chronotherapeutic drug delivery system of torsemide

The objective of this study was to prepare and evaluate chronotherapeutic drug delivery systems (ChrDDs) of torsemide. Compression coated tablets (CCT) containing torsemide in the core tablet were prepared by the compression coating technique with different grades of polyethylene oxide (PEO WSR 301 & 1105). The optimized formulations were characterised for tabletting parameters and drug polymer interaction by Fourier-Transform Infrared Spectroscopy (FTIR).The hardness of all the CCT using PEO WSR 301 & PEO WSR 1105 were in the range 6-8 kg/cm2 & 5.5 to 7 kg/cm2 respectively. Their friability values were 99%. The FTIR studies showed no interaction throughout the process of development. Formulations of F7 and of P7 were considered optimized formulations since they yielded a predetermined lag time of 6h before burst release. Hence, these formulations can be exploited to achieve chronotherapeutic drug delivery systems of Torsemide for the treatment of hypertension at the time the patient needs it.

A Biphasic Release System of Lornoxicam Based on “Tablets in Capsule” Device

The aim of the present investigation is to obtain a programmed drug delivery from a novel system containing a fast release and prolonged release tablet (PRT) placed into a capsule to achieve the biphasic release pattern of lornoxicam. Fast release tablets (FRT) with 3.25 mg were prepared with different diluents and varying concentrations of disintegrant and binders. Hydrogenated castor oil and hydrogenated vegetable oil are used to modulate drug release for the development of PRT with a 12.25 mg dose calculated as a zero-order principle. The compressed tablets were evaluated for various physicochemical parameters like hardness, friability, drug content uniformity, weight variation and in-vitro drug release studies. The optimized FRT and PRT tablets were placed in the size 2 capsule to attain biphasic release in which the immediate rapid release was obtained by the FRT followed by slow release from the PRT for 24 hours. The optimized ‘tablet in capsule’ (TCHV) (containing 3%w/w of HVO) followed first-order release with a Non-Fickian diffusion mechanism. FT-IR studies revealed no interaction between the drug and polymers. There were no marketed dosage forms of lornoxicam with biphasic release; hence, the present study indicated the applicability of the ‘tablets in capsule’ technique in the design of biphasic release systems of lornoxicam.

Dissolution rate enhancement of bicalutamide by adsorption process

The aim of the present research was to enhance the dissolution rate of poorly water soluble drug, bicalutamide by adsorption process. Bicalutamide is an antiandrogen agent used in the treatment of prostate cancer. To improve the dissolution rate of the drug, hydrophilic carrier like povidone K30 and adsorbent like magnesium aluminum silicate were used as dissolution rate enhancers. Granules of bicalutamide were prepared by wet granulation technique by using magnesium aluminum silicate and povidone K 30 either alone or in combination at different concentrations. The granules were evaluated for packing and compression properties. The granules were compressed into tablets, and different tableting parameters were investigated. The dissolution profile of the tablets was also evaluated and compared with the marketed product. From the dissolution profile, it was observed that the carrier ratio of 3:1 of magnesium aluminum silicate to povidone K 30 exhibited higher dissolution rate than the other formulations.