QUICK/SLOW BIPHASIC RELEASE OF A POORLY WATER SOLUBLE ANTIDIABETIC DRUG FROM BI-LAYER TABLETS

Objective: The objective of the present work is to develop a bi-layer tablet consisting of an Immediate Pulse Release [IPR] layer and a sustained release [SR] layer that can produce a distinct biphasic release having two different drug release rates. The IPR layer is intended to release a fraction of the dose rapidly at a faster rate and the SR layer is meant for slow release of the remaining dose at a slower rate for a desired period of time.Methods: The quantitative determination was carried out by UV spectrophotometer. Solid dispersion was prepared by melt method. IPR layer was prepared by direct compression method, SR layer was prepared by wet granulation method. In-vitro drug release study from tablets was carried out in USP II tablet dissolution rate test apparatus. FTIR, DSC, XRD studies were performed.Results: 89% of the incorporated drug was released within 30 min in acid solution of pH 1.2 from the IPR tablet prepared with the highest amount of gelucire due to solid state transformation of the drug. The SR layer (SR8) comprising of SAL, CG and CMC produced prolonged drug release (70% in 10 h). The optimized IPR3 layer and SR layers were compressed to form bi-layer tablets from which 23-37% drug was released immediately in 30 min, and the remaining drug was released slowly for 7 to 10 h depending upon the compositions of the tablets.Conclusion: This study revealed that bi-phasic release of GPZ consisting of an initial quick release and subsequent slow release could be achieved by formulating bi-layer tablets using the existing tablet technology, and such formulation may be able to control hyperglycaemia effectively for a longer period of timeÂ

FACTORS INFLUENCING DELAYED RELEASE FOLLOWED BY RAPID PULSE RELEASE OF DRUGS FROM COMPRESSION COATED TABLETS FOR COLON TARGETING

Objective: This work was undertaken to develop colon targeted tablets that can minimize premature release of ibuprofen (IBP) and metronidazole (MNZ) in a lag period of 7h during which the tablets are likely to remain in the upper gastro-intestinal tract, and produce rapid pulse release within 1-5 h after the lag period when the tablets could be located in the colon with or without intervention of colonic microflora.Methods: Core tablets of ibuprofen and metronidazole containing different amounts of tri-sodium citrate (TSC) as osmogen were compression coated with locust bean gum (LBG) and carboxymethyl LBG (CMLBG). In vitro drug release studies were performed in a dynamic pH shift condition with or without rat cecal matters. The release of the drugs were also monitored at different hydrodynamic conditions.Results: In vitro release studies revealed that increase in the amount of TSC, decrease in coat-weight and change in hydrodynamic conditions influenced the drug release considerably. While LBG coated tablets under the stated conditions failed to provide complete release of the drugs in 12 h, CMLBG coated tablets produced complete release rapidly in the post lag period minimizing the release in the initial 7 h. Presence of rat cecal matter in dissolution medium further accentuated the release of the drugs from CMLBG compression coated tablets in the post lag period.Conclusion: The study revealed that tablets containing appropriate amount of osmogen in the core and compression coated with suitable amount of CMLBG may be suitable for colon targeting of drugs even in the absence of colonic microflora

Priprava i in vitro karakterizacija alginatnih nanokapsula za polagano oslobađanje testosterona

Slow release testosterone-loaded nanocapsules in alginate, biodegradable hydropolymer, were prepared by in situ nanoemulsion-polymer crosslinking approach. Different formulations varying in the drug loading solvent phase were prepared. Four different drug-loading solvents were assayed and the food grade hexane provided nanocapsules testosterone load of 30%. Testosterone loading was confirmed by FT-IR, DSC and quantitated by HPLC. Prepared nanocapsules appeared spherical with a dense drug core in transmission electron microscopy studies. Hydrodynamic diameter of nanocapsules was 34.5 ± 1.7 nm, with a Gaussian distribution and the zeta potential –5.0 meV. Sustained diffusive drug release was observed in vitro, following zero order kinetics releasing the drug payload over a period of 48 hours. Embedding testosterone in alginate provided sustained release. Different drug loading solvents have distinct influence on drug loading and nanocapsules size distribution. The nanocapsulation technique developed can be a good choice for the development of different sustained steroid hormonal drug carriers.U radu je opisana priprava nanokapsula za polagano oslobađanje testosterona. Nanokapsule su pripravljene iz biorazgradljivog hidrofilnog polimera alginata umrežavanjem in situ. Varirajući udio lijeka u tekućoj fazi pripravljeno je nekoliko različitih nanokapsula. Upotreba heksana kao otapala omogućila je visoki sadržaj testosterona u nanokapsulama (30%). Prisutnost testosterona potvrđena je pomoću FT-IR i DSC, a za kvantitativno određivanje upotrebljena je HPLC metoda. Pomoću transmisijskog elektronskog mikroskopa utvrđeno je da su pripravljene nanokapsule sferno simetrične i imaju gustu ovojnicu s ljekovitom supstancijom. Hidrodinamički promjer nanokapsula bio je 34,5 ± 1,7 nm (Gaussova raspodjela), a zeta potencijal –5,0 meV. Oslobađanje testosterona in vitro bilo je polagano tijekom 48 sati, a slijedilo je kinetiku nultog reda. Otapalo koje je upotrebljeno za punjenje nanokapsula ljekovitom tvari utječe na količinu ljekovite tvari i raspodjelu veličine nanokapsula. Opisana metoda nanokapsuliranja može se primijeniti i na druge steroidne hormone

Razvoj i vrednovanje mikrospužvastih sustava etilceluloze i ksantan gume za kontroliranu perkutanu isporuku diklofenak natrija

In this study, xanthan gum-facilitated ethyl cellulose microsponges were prepared by the double emulsification technique and subsequently dispersed in a carbopol gel base for controlled delivery of diclofenac sodium to the skin. Scanning electron microscopy revealed the porous, spherical nature of the microsponges. Increase in the drug/polymer ratio (0.4:1, 0.6:1, 0.8:1, m/m) increased their yield (79.1–88.5 %), drug entrapment efficiency (50.0–64.1 %), and mean particle diameter (181–255 µm). Compared to the microsponges with high drug/polymer ratio (0.8:1, m/m), the flux of entrapped drug through excised rat skin decreased by 19.9 % and 17.0 %, respectively, for the microsponges prepared at low and intermediate drug/polymer ratios. When an equivalent amount of pure drug (not entrapped into microsponges) was dispersed into the gel base and the flux was compared, the microsponges (drug/polymer ratio 0.8:1, m/m) were found to reduce the flux by 33.3 %. Whether the drug was dispersed either in un-entrapped or entrapped form into the gel base, the drug permeation through rat skin followed Higuchi\u27s diffusion kinetic model. The microsponges prepared at the lowest drug/polymer ratio exhibited a comparatively slower drug permeation profile and were hence considered most suitable for controlled drug delivery application. FTIR spectroscopy and DSC analyses indicated the chemically stable, amorphous nature of the drug in these microsponges. The gel containing these optimized microsponges was comparable to that of a commercial gel formulation and did not show serious dermal reactions. Hence, the microsponge system obtained at the lowest drug/polymer ratio could be useful for controlled release of diclofenac sodium to the skin.U radu su opisani mikrospužvasti sustavi s etilcelulozom i ksantan gumom pripravljeni metodom dvostruke emulzifikacije i dispergirani u podlogu s karbopol gelom za kontrolirano oslobađanje diklofenak natrija na kožu. Elektronska pretražna mikroskopija potvrdila je poroznu, sferičnu strukturu mikrospužvastih sustava. Povećanjem omjera lijeka i polimera (0,4:1, 0,6:1, 0,8:1, m/m) povećalo se iskorištenje (79,1–88,5 %), količina uklopljenog lijeka (50,0–64,1 %) i srednji promjer čestica (181–255 µm). Prolaz uklopljenog lijeka kroz izrezane komade kože štakora smanjio se za 19,9 %, odnosno 17,0 %, kada se omjer lijeka i polimera smanjio s visokog (0,8:1, m/m) na niski i srednji. Oslobađanje iz mikrospužvastih struktura s omjerom lijeka i polimera 0,8:1 (m/m) smanjeno je za 33,3 % u odnosu na oslobađanje ekvivalentne količina lijeka koji nije uklopljen već samo dispergiran u geliranu podlogu. Ako je lijek bio dispergiran kao neuklopljen ili kao uklopljen u geliranu podlogu, permeacija lijeka kroz kožu štakora slijedila je Higuchijev difuzijski kinetički model. Mikrospužvaste strukture pripravljene uz najniži omjer lijeka i polimera pokazale su sporiji permeacijski profil pa ih smatramo najpovoljnijima za kontrolirano oslobađanje lijeka. FTIR spektroskopija i DSC analiza pokazale su da je lijek u mikrospružvastim sustavima stabilan i amorfan. Gel s optimiranim mikrospužvastim sustavom sličan je komercijalnom gelu i ne pokazuje ozbiljne kožne reakcije. Sustav pripravljen s najnižim omjerom lijeka i polimera mogao bi biti pogodan za kontrolirano oslobađanje diklofenak natrija na kožu

pH dependent chemical stability and release of methotrexate from a novel nanoceramic carrier

Considering the pH dependent chemical stability of anticancer drug methotrexate (MTX), the present communication reports a new approach for intercalation of the same in a nanoceramic vehicle, magnesium aluminium layered double hydroxide (LDH), by ex situ anion exchange method at pH 7.00, using 0.3 M ammonium acetate solution for dissolution of the drug. This simple method ensures maximum stability of the drug at the above said pH, with no degradation byproduct (e.g., N-10-methyl folic acid formed due to alkaline hydrolysis) under the given experimental conditions, compared to the similar approach, using 0.1 M sodium hydroxide solution, reported in our earlier work. Importantly, the above method leads to an enhanced drug loading of 32.3 wt%, compared to our previous reports. The cumulative release profile of MTX from LDH-MTX formulation in phosphate buffer saline (PBS) at pH 7.4 exhibited burst release initially which was taken care of by imparting a unique coating of poly(D,L-lactideco-glycolide, PLGA) on the LDH-MTX nanostructure that reduces the toxicity due to local accumulation. Hence, the superiority of the above for use in cancer chemotherapy, over the conventional drug-polymer system has been established w.r.t the drug release profile and a possible hypothesis of the same has been suggested. The half maximal inhibitory concentration (IC50) of the MTX drug used in this study has been determined and the same has been used to estimate the time dependent (24, 48, 72 and 96 h) efficacy of the MTX loaded samples with/without polymer coating, on human colon tumour cells (HCT-116)

Development and effect of different bioactive silicate glass scaffolds: In vitro evaluation for use as a bone drug delivery system

Local drug delivery systems to bone have attracted appreciable attention due to their efficacy to improve drug delivery, healing and regeneration. In this paper, development and characterization of new formulations of bioactive glass into a porous scaffold has been reported for its suitability to act as a drug delivery system in the management of bone infections, in vitro. Two new glass compositions based on SiO2-Na2O-ZnO-CaO-MgO-P2O5 system (BGZ and MBG) have been developed which after thorough chemical and phase evaluation, studied for acellular static in vitro bioactivity in SBF. Porous scaffolds made of these glasses have been fabricated and characterized thoroughly for bioactivity study, SEM, XRD, in vitro cytotoxicity, MTT assay and wound healing assay using human osteocarcoma cells. Finally, gatifloxacin was loaded into the porous scaffold by vacuum infiltration method and in vitro drug release kinetics have been studied with varying parameters including dissolution medium (PBS and SBF) and with/without impregnation chitosan. Suitable model has also been proposed for the kinetics. 63-66% porous and 5-50 pm almost unirnodal porous MBG and BGZ bioactive glass scaffolds were capable of releasing drugs successfully for 43 days at concentrations to treat orthopedic infections. In addition, it was also observed that the release of drug followed Peppas-Korsmeyer release pattern based on Ficldan diffusion, while 0.5-1% chitosan coating on the scaffolds decreased the burst release and overall release of drug. The results also indicated that MBG based scaffolds were bioactive, biocompatible, noncytotoxic and exhibited excellent wound healing potential while BGZ was mildly cytotoxic with moderate wound healing potential. These results strongly suggest that MBG scaffolds appear to be a suitable bone drug delivery system in orthopedic infections treatment and as bone void fillers, but BGZ should be handled with caution or studied elaborately in detail further to ascertain and confirm the cytotoxic nature and wound healing potential of this glass. (C) 2014 Elsevier Ltd. All rights reserved