Korsemeyer-Peppas Model Research Articles

FORMULATION OPTIMIZATION AND EVALUATION OF GASTRORETENTIVE TABLETS OF ONDANSETRON HCL

The aim of the work is to design Gastroretentive tablets of Ondansetron HCl for gastric retention by using 32 factorial designs. Floating tablets of Ondansetron HCl were prepared by direct compression method using polymers, sodium alginate and excipient. Gastroretentive tablets of Ondansetron HCl were successfully prepared by effervescent technique using different gel forming polymers- HPMC K200M, and sodium alginate. Formulation was optimized by design expert software. Floating tablets were evaluated for floating time, floating lag time, drug content, raft measurement and in vitro dissolution profile. The lag time is between 17-22 sec and floating time of the formulations for 12 hrs. The best fit model is Korsemeyer Peppas Model. From the study it is proof that the sustain release by floating tablets of Ondansetron HCl can be develop. Optimized batch selected was A3, The prepared gastroretentive test formulation was found to exhibit satisfactory physico-chemical characteristics at the end of 3 months, during the stability studies. The optimized formulation A3 was found to be stable at 400C/ 75% RH. Keywords: Gastric retention time, Ondansetron HCl, HPMC, sodium alginate, measurement of raft, Factorial design, stability studies.Â

Hollow chitosan nanocomposite as drug carrier system for controlled delivery of ramipril

Hollow biodegradable polymer nanoparticles as drug carrier possess effective low density and higher surface area. Chitosan hollow nanospheres were prepared using poly-D,L-lactide-co-glycolide as template by single emulsion method. The DLS studies showed increase in size from 125 nm to 186 nm for the formation of core@shell structure. The BET surface area increased from 62 m2 g−1 for chitosan@poly-D,L-lactide-co-glycolide to 111 m2 g−1 for hollow chitosan nanospheres. TEM analyses indicated core@shell, chitosan@poly-D,L-lactide-co-glycolide and the hollow morphology of the chitosan nanospheres. Ramipril in acetone (1.5 mg/mL, 3 mg/mL and 5 mg/mL) was physically adsorbed onto hollow chitosan nanospheres and the amount of adsorbed ramipril was determined by HPLC. Higher entrapment efficiency (91%) with 96% of the drug content was observed for the sample with 5 mg/mL of the drug. The in-vitro release of ramipril of 86% and 73% was achieved in acetate (pH-3.3) and phosphate (pH-6.3) buffers respectively while only 48% of ramipril in Tris buffer (pH-8.0) medium. Korsemeyer-Peppas model of drug release indicated the release of ramipril being swelling controlled.

Dietary supplements containing vitamins and minerals: Formulation, optimization and evaluation

ABSTRACT The regular diet of common man is often deficient in certain nutrients, so dietary supplements are commonly prescribed. In this study, a combination of vitamins and minerals in the form of a bilayer tablet is proposed as a dietary supplement. A film-coated bilayer tablet in which one layer contains premixed vitamins (A, D, E, C, B1, B2, B3, B5, B6, B7, B9 and B12) and the other layer contains premixed minerals (magnesium, manganese, molybdenum, iodine, zinc, silicon and copper) was formulated by direct compression method. This uniquely formed bilayer tablet was assessed for physiochemical properties, microbial load and stability studies. FTIR studies revealed that there was no interaction between the vitamins, minerals and excipients used in the study. In vitro dissolution test revealed that >85% of folic acid and zinc sulphate were released in 60 min at pH 6.5–7.5. The release of folic acid was found to follow a first-order and Higuchi model, whereas zinc sulphate followed a first-order and Korsemeyer-Peppas model, indicating diffusion and erosion mechanism. The results of the long term and accelerated stability studies showed that, there were no changes in physicochemical properties and release pattern of bilayer tablets. Furthermore, the optimized formulation showed increase in the stability period for about 24 months. This nutritional supplement based on oral delivery of bilayer tablets is expected to gain more acceptance among the commercially available products due to better release properties and combination therapy.

Fabrication and Evaluations of Dual Crosslinked Mesalamine containing Pectin-Chitosan gel micro beads for controlled and targeted colon delivery

Objectives: The aim of the present work was to prepare and characterize mesalamine loaded microbeads (MLM) consisting of optimized ratios of chitosan and pectin polysaccharides using ionic gelation technique for management of inflammatory bowel disease. Methodology: Mesalamine loaded microbeads were prepared using ionotropic gelation method that was double cross linked with calcium chloride (3-6%, w/v) and sodium sulphate (2-4%, w/v) solutions. The formulation was optimized with the help of two levels and three factors factorial design method. The optimization parameters selected for formulation variables were viz., pectin-chitosan ratio, calcium chloride-sodium sulphate ratio and curing time. The prepared formulations were further characterized on the basis of particle size, shape, swelling index, entrapment efficiency, and percentage yield and in vitro drug release studies. The in vitro release studies using rat caecal content (2 and 4 % w/v) was also performed to simulate the human colonic condition. Results: The mean particle size, entrapment efficiency and percentage yield of MLM were ranged from 875.45 to 975.45 µm, 72.2 to 86.7% and 93.6 to 97.9% respectively. The swelling index of MLM formulations revealed lesser into acidic medium, while augmented swellings were found to be at pH 6.8 and 7.2 respectively. The swelling degree was found to be 7.34 to 13.88% into SIF at pH 6.8 whereas, intensely swelled was 16.24 to 46.02% into SCF at pH 7.2 during 8 h studies. In vitro drug release profile of MLM exhibited that only 1.28 to 4.42 drug was released at simulated gastric fluid (SGF, pH 1.2, 2 h), however optimum drug released was found into simulated intestinal fluid (SIF, pH 6.8, 3 h) i.e. 5.33 to 31.33% and into simulated colonic fluid (SCF, pH 7.2, 18 h) i.e. 32.13 to 87.12% correspondingly. Scanning electron microscopy (SEM) revealed that the microbeads were consisting of semispherical and wrinkled rough surfaces. Further, the rat caecal contents (2 and 4% w/v) release studies confirmed for complete polymeric degradation by colonic enzymes. The release kinetics and mathematical modeling studies carried out for optimized formulation shown that the optimized formulations were of non fickian mechanism (n=0.49 to 0.74) type governed by both diffusion and erosion controlled following Higuchi and Korsemeyer peppas model fittings. Conclusion: It can be concluded from the study that the optimized MLM formulations may be effective for colon targeting and treating inflammatory bowel disease.

Desloratadine-Eudragit® RS100 Nanoparticles: Formulation and Characterization.

The objective of the present study was to formulate Desloratadine-Eudragit® RS100 nanoparticles and investigate the characteristics of the prepared nanoparticles. The nanoparticles were prepared by spray drying method and the quantification of desloratadine (DL) was carried out with a high performance liquid chromatography (HPLC) method. DL was successfully loaded to polymer and the developed HPLC method was found to be linear, reproducible, precise, accurate, specific and selective. Characterization of the nanoparticles including entrapment efficiency, particle size, zeta potential, morphology, polidispersity index, solid state characterizations and drug release was performed. In vitro release studies of DL loaded nanoparticles were also examined in the simulated intestinal fluid (pH 7.4). In vitro release of DL from nanoparticle formulations followed Korsemeyer-Peppas model. A validated HPLC method was developed for the determination of DL. Proposed spray drying method can be successfully applicable to the nanoparticle preparation containing DL. In addition, the release studies of all nanoparticles and active substance have been studied comparatively. Hence, it could be concluded that DL loaded nanoparticles seem to be a promising drug delivery system for the active agent.

Layer-by-layer assembly of hyaluronic acid/carboxymethylchitosan polyelectrolytes on the surface of aminated mesoporous silica for the oral delivery of 5-fluorouracil

The aim of the present work is to develop the polyelectrolyte complexes (PEc) coated on the surface of aminated mesoporous silica nanoparticles (AMSN) through layer by layer (LbL) assembly for the controlled delivery of 5-fluorouracil (5-FU). The polyelectrolyte complexes coated aminated mesoporous silica nanoparticles were characterized by FTIR, XRD, DLS, SEM, TEM and NMR. The optimum pH value for the encapsulation of 5-FU into AMSN-HA/CMC (AMSN-PEc) was found to be 5.4. The controlled release behavior of 5-FU was examined with two different pHs at 1.2 and 7.4. The release rate of the loaded drug molecules was high and controlled level at stimulated intestinal pH 7.4 but decreased considerably at gastric pH 1.2. Release data were fitted to empirical equations to understand the nature of drug release profiles. The drug release profile followed Korsemeyer-Peppas model. The cytotoxicity of 5-FU loaded (AMSN-PEc) towards HT-29 and L929 cells was investigated. The results showed that 5-FU loaded AMSN-PEc retained significant antitumor activities. This study demonstrated that the prepared drug delivery system (DDS) has potential application as a drug carrier. The intracellular uptake of the drug loaded drug delivery system was confirmed by Confocal Raman microscopy.

FORMULATION AND EVALUATION OF IN-SITU GEL CONTAINING CIPROFLOXACIN HYDROCHLORIDE IN THE TREATMENT OF PERIODONTITIS.

Objective: The present study describes the use of in-situ gel in periodontal drug delivery systems which contains gellan gum (0.4–0.6% w/v), pluronic F127 (14, 15 and 16% w/v), and drug Ciprofloxacin HCl (0.1% w/v). Number of peoples around the world suffered from dental problem and ultimate fear is tooth loss hence in-situ gelling system was designed for the treatment of periodontal diseases. The therapeutic efficacy of drug can be greatly improved by prolonging its contact time.Methods: Formulations were developed by simple solution method. Each formulation was characterized in terms of in gelling strength, viscosity, rheology, content uniformity, in vitro drug release, and syringeability.Results: In vitro gelation time and the nature of the gel formed in simulated saliva for prepared formulations showed polymeric concentration dependency. Drug release data from all formulations was fitted to different kinetic models and the Korsemeyer-Peppas model was the best fit model. Drug release was significantly decreased as the concentration of each polymer component was increased. Increasing the concentration of each polymeric component significantly increased viscosity, syringeability, and time for 50%, 70%, and 90% drug release. In conclusion, the formulations described offer a wide range of physical and drug release characteristics. The formulation containing 0.6% w/v of gellan gum and 14% w/v of pluronic F127 exhibited superior physical characteristics. The formulation stored at 4˚C before application, which is syringeable through 21 gauge needle.Conclusion: This formulation was made to inject directly in to periodontal pocket where it immediately converts in to gel form at body temperature.

Formulation and In vitro Evaluation of Floating Microspheres of Misoprostol

Misoprostol is a synthetic prostaglandin PGE1 analogue, which has proved to be an effective anti-secretory agent for oral use. The major indications of Misoprostol are in the prevention and treatment of NSAID-induced gastric and duodenal ulcers. Its half-life is 20-40 minutes. More than one third of patients with ulcers are resistant to H2 antagonists. So, these patients can be healed on Misoprostol. The objective of the present study was to formulate gastroretentive floating drug delivery system of an antiulcer drug Misoprostol. Floating microspheres of Misoprostol were prepared by an emulsification solvent evaporation technique using hydroxy propyl methyl-cellulose (HPMC K 100M) and ethyl cellulose. The percentage yield and drug entrapment efficiencies of these floating microspheres were within the range between: 70 ± 2.8 to 98 ± 2.9 % and 39.27 to 82.39 %, respectively. The determined mean particle size for all the microspheres were 250 ± 7.28 to 400 ± 2.32 µm. The flowability of these microspheres was found good. A high performance liquid chromatography (HPLC) method with ultra-violet (UV) detection was selected for the method of analysis. The drug release was found to delay for 12 hours with the increasing drug to polymer ratio. The drug release kinetics followed Korsemeyer-Peppas and Higuchi model with anomalous (non-Fickian) diffusion mechanism for the drug release. The FTIR and DSC studies showed that there was an absence of chemical interaction between the drug and the excipients. The in vitro drug release from Misoprostol floating microspheres showed the drug release was dependent on the drug to polymer ratio. The drug release was found delayed with the increasing drug to polymer ratio.

Colon targeted drug release studies of 5-ASA using a novel pH sensitive polyacrylic acid grafted barley

In this investigation, we have reported novel polyacrylic acid grafted barley (BAR-g-PAA) in the presence of ceric ammonium nitrate (CAN) as an initiator using microwave radiation (MW). The different grades of grafted materials have been synthesized by varying the amount of reaction parameters and best grade is optimized on the basis of percentage grafting. The prepared novel grafted materials are confirmed by various physicochemical analyses like FTIR, XRD analysis, elemental analysis, SEM morphology and DSC studies. The swelling of different matrix tablets has been studied at 25 and 37 °C by varying pH environment (i.e. 1.2 and 7.2) similar to GI tract. An ideal matrix tablet has been prepared for the controlled drug release study at 37 °C in different dissolution medium like pH = 1.2 and 7.2. The mechanism and kinetics of 5-amino salicylic acid (5-ASA) from matrix tablet has been evaluated by Korsemeyer–Peppas model.

Naproxen-Gelucire Nanoformulations for Improved Solubility and Dissolution Rate of Poorly Water-Soluble Drug Naproxen

Naproxen-Gelucire Nanoformulations (NFs) in terms of their phase solubility behavior, physico-chemical characteristics, cytotoxicity and morphology and dissolution enhancement has been studied using the poorly water soluble drug, naproxen. The NFs were prepared via wet milling using a conventional Retsch Planetary ball mill in various ratios of drug to polymer (1:1, 1:2, 1:3, 1:4). The release rate of naproxen from various ratios of drug/polymer nanoparticles was investigated using USP paddle apparatus (type II). A comparative phase solubility of naproxen was performed in different carrier concentrations of simulated gastric fluid (pH 1.2) and simulated intestinal fluid (pH 6.8). The highest dissolution enhancement was achieved for the formulation with ratio of 1:4. This is a 160% enhancement when compared to that of the pure drug. The ability of amphiphillic surfactant carriers to accelerate in vitro dissolution of poorly water-soluble drugs has been attributed to wetting, micellar solubilization, and/or deflocculation. The Korsemeyer–Peppas model most aptly fits the in vitro dissolution data and gives an insight into the possible drug release mechanisms predominated by anamolous non-Fickian diffusion. Thus, the nanoformulations studied can help improve the physicochemical characteristics of naproxen towards its dissolution enhancement and possibly will increase the oral bioavailability of the drug without any adverse cytotoxic consequences.

Design, characterization and in vitro evaluation of HPMC K100 M CR loaded Fexofenadine HCl microspheres.

The aim of the current study was to formulate Fexofenadine hydrochloride loaded sustained release microspheres using HPMC K100 M CR, a release retardant hydrophilic polymer by solvent evaporation method. The effect of different drug loading on drug content, drug encapsulation efficiency and release of drug was monitored. The studies on in vitro release mechanism were performed using USP paddle method with 900 ml of phosphate buffer (pH 6.8) for 10 h at 100 rpm. The mechanism of the drug release was determined by fitting in vitro release data to various release kinetic models such as the zero order, first order, Higuchi, Hixson Crowell and Korsemeyer–Peppas model and finding R2 values for the release profile corresponding to each model. The results confirm that the release rate of the drug from the microspheres is highly affected by the drug to polymer ratio. The study finds that Higuchi release kinetics, Korsmeyer–Peppas release kinetics and Hixson–Crowell release kinetics were the major release mechanism. The release mechanism was found to be non-Fickian with increase of polymer content. Scanning electron microscopic technique was performed to obtain the morphological changes due to different drug loading. Differential scanning calorimetry and Fourier transform infra-red spectroscopy was performed to determine any interaction of drug with the polymer. A statistically significant variation in release rate was observed for variation in the amount of HPMC K100 M CR. In the present study, a series of sustained release formulations of Fexofenadine hydrochloride were developed with different drug loading so that these formulations could further be evaluated from the in vivo studies. The formulations were found to be stable and reproducible.

Introduction to Editorial Board Members: Prof Nicholas A. Peppas

Introduction to Editorial Board Members: Prof Nicholas A. Peppas

Preparation, Optimization and Characterization of Eudragit Coated Chitosan Piroxicam Microspheres Intended for the Treatment of Rheumatoid Arthritis

As a novel drug delivery approach, piroxicam an anti rheumatoid drug is loaded in microspheres prepared by chitosan as a polymer and coated with eudragit S-100 to prepare colon specific microspheres which increases the bioavailability of the drug to the targeted area and in a controlled manner and reduces GI related side effects. In the present study chitosan microspheres were prepared using emulsion crosslinking technique, glutaraldehyde as a crosslinker and microencapsulation using phase coacervation technique. Optimization is done by varying drugpolymer ratio (1:2 to 1:8), emulsifier concentration, i.e., span 80 (0.5 ml, 0.75 ml, 1 ml), stirring speed (500 rpm, 1000 rpm, 1500 rpm, 2000 rpm, 2500 rpm), cross-linker concentration (2.5 ml, 5 ml, 10 ml) and coat-core ratio from 1:2 to 1:6. The prepared chitosan microspheres showed high entrapment efficiency about 97.29% with percent yield 90.26. In the present study FTIR studies confirmed the absence of interactions between the pure drug, i.e., piroxicam and the excipients used. SEM images revealed that the prepared chitosan microspheres were spherical in shape with rough surface and particle size ranged from 90.21 to 172 μm. Showed good drug release profile for both coated and uncoated chitosan piroxicam microspheres of about 86% and 96%. Drug release kinetics showed that microspheres followed korsemeyer peppas model indicating the drug diffusion mechanism from polymer matrix.

Formulation and in vitro evaluation of a fast-disintegrating/sustained dual release bucoadhesive bilayer tablet of captopril for treatment of hypertension crises.

Hypertension crisis is one of the main health problems and its effective treatment is of high importance. For this purpose, fast-disintegrating and sustained release formulations of captopril, as a drug of choice, were prepared using conventional mucoadhesive polymers hydroxypropyl methylcellulose (HPMC), sodium carboxymethyl cellulose (Na-CMC), hydroxypropyl cellulose (HPC), Carbopol 934 (CP934) and sodium alginate (Na-alg). The optimum sustained release formulations were selected based on mean dissolution time (MDT). The swellability and mucoadhesive properties of selected formulations were assessed and compared. A direct relationship between swelling and release rates/adhesiveness of sustained release formulations was observed. The results showed that formulations containing combination of CP934 and cellulose-based polymers had the highest swellability, sustainability and adhesion strength. These formulations prolonged drug release up to 8 h showing good fitness to Korsemeyer-Peppas model. Moreover, the adopted fast-disintegrating tablet could release up to 100% of drug within 3 min in oral pH. Finally, a dual fast-disintegrating/sustained release bucoadhesive bilayer tablet consisting of optimized formulations was prepared releasing 30% of the drug initially within 15 min and the remaining up to 8 h which could be considered as an appropriate formulation for the treatment of hypertension crises.

Formulation and Evaluation of Buccoadhesive Tablets of Losartan Potassium

The present investigation is concerned with formulation and evaluation of buccoadhesive tablets containing antihypertensive drug, Losartan Potassium to avoid the first pass effect and to improve its bioavailability with reduction in dosing frequency and dose related side effects. The tablets were prepared by wet granulation method. Nine formulations were developed with varying concentrations of polymers like hydroxypropylmethyl cellulose K100 and Guar gum. The tablets were tested for hardness, friability, weight variation, content uniformity, surface pH, swelling index, ex vivo mucoadhesive strength, in vitro drug dissolution study and ex-vivo permeation study. FTIR and DSC studies showed no evidence on interactions between drug and excipients. The in vitro release of Losartan Potassium was performed under sink conditions. The mucoadhesive strength of formulation F9 was found to be 0.14307 N. The swelling index of formulation F9 was found to be 87%. The formulation F9, containing 25 mg of losartan potassium exhibited 6 h sustained drug release of 96% with desired therapeutic concentration. The in vitro release kinetics studies revealed that all formulations fits well with zero order kinetics followed by Korsemeyer-Peppas model and the mechanism of drug release is Non-Fickian diffusion. Based on the results of ex vivo mucoadhesive strength and swelling index studies formulation F9 was selected as optimized formulation and subjected for stability study. Short-term stability studies on the promising formulation indicated that there are no significant changes in drug content and in vitro dissolution characteristics.

Synthesis, characterization of thiolated karaya gum and evaluation of effect of pH on its mucoadhesive and sustained release properties

Present study aims at synthesis and characterization of thiolated gum karaya by reacting karaya gum with 80% thioglycolic acid resulting in esterification and immobilization of thiol groups on polymeric backbone. Immobilized thiol groups were found to be 5.026mM/g determined by Ellman's method. It was characterized by FTIR, DSC and XRD. Directly compressible tablets prepared using thiolated gum displayed more disintegration time, swelling and mucoadhesion with increase in pH of medium simulating gastric and intestinal environment than plain gum. Controlled drug release for more than 24h by Fickian diffusion following Korsemeyer-Peppas model was observed with Metoprolol Succinate as a model drug as compared to plain gum which released more than 90% of the drug within 2h. Synthesized thiomer showed no cytotoxicity determined using HepG2 cell line. According to these results, thiolated gum karaya seems to be promising excipient for the development of mucoadhesive drug delivery systems.

Preparation and evaluation of once-daily sustained-release coated tablets of tolterodine-l-tartrate

In this study, once-daily, sustained-release matrix tablets of tolterodine l-tartrate (TOL) for treatment of overactive bladder (OAB) were prepared by direct compression using various amounts of hydrophilic polymers such as HPMC 2910 and HPMC 2208 along with other tablet excipients; the tablets were then coated. In vitro dissolution studies were carried out under different pH conditions. The dissolution data were fitted into zero-order, first-order, Higuchi and Korsemeyer-Peppas models to identify the pharmacokinetics and mechanism of drug release. Among the four formulations (F1-F4), the dissolution profiles of formulation F2 were most similar to the marketed product with similarity and difference factors of 70.25 and 1.59 respectively. Furthermore, pharmacokinetic studies were carried out in healthy human volunteers after oral administration of the prepared TOL sustained-release matrix-coated tablet and the marketed product. The results revealed that the pharmacokinetic parameters of AUC, Cmax, Tmax, t1/2, Kel, and MRT of TOL for the developed formulation (F2) were not significantly different from that for the marketed product, suggesting that they were bioequivalent. Therefore, the developed sustained-release tablet formulation of TOL could be an alternative dosage form to the SR capsule for treatment of OAB.

Development, in vitro and in vivo characterization of Eudragit RL 100 nanoparticles for improved ocular bioavailability of acetazolamide

Glaucoma is characterized by increased intra ocular pressure (IOP) which results in blindness if left untreated. Acetazolamide (ACZ) is used to treat glaucoma since long back. Since it is a Class IV drug [According to Biopharmaceutics Classification System (BCS)], so its topical delivery results in poor ocular bioavailability. Objective of the present study is to increase the topical ocular bioavailability and to sustain the release of drug for longer time. ACZ-loaded Eudragit® RL 100 nanoparticle suspension (ACZ-E-NPs) was prepared by the nanoprecipitation method. Ratio of organic to aqueous phase and composition of organic phase were altered to get the best formulation. Formulations prepared with acetone and methanol as organic phase were smallest in size. EE was in the range of 57.8% to 68.5%. According to drug release study almost all the formulations released 80% of drug in 8 h duration. The kinetics of drug release showed that the drug release pattern followed Higuchi’s model (highest R2 values) and further it was fitted to the Korsemeyer–Peppas model, which showed the release was as per Fickian diffusion. IOP lowering effects of plain drug solution and ACZ-E-NPs were compared in adult male albino rabbits with a Riester Tonometer. The data revealed that the ACZ-E-NPs lower the IOP for longer time and of higher magnitude also. The difference was significant (p < 0.001). Short-term stability study showed that none of the formulations was having remarked difference in their physicochemical properties after 6 months of storage at various temperatures.

Improvement of Solubility and Dissolution Rate of Sirolimus by Solid Dispersions in Combination with Surface Adsorbent

Sirolimus has a poor solubility in water ranging from 2-6 µg/mL. The mean bioavailability is approximately 14%. The present study was carried out with a view to enhance the dissolution rate of poorly water-soluble drug sirolimus using Gelucire® as carriers and lactose monohydrate as an adsorbent. A combination of melt and adsorption techniques was employed for the preparation of solid dispersions (SD) to make final product free flowing. Phase solubility study was conducted to evaluate the effect of carriers on aqueous solubility of sirolimus. In order to elucidate the mechanism of dissolution enhancement, solid state characteristics were investigated using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD). Mathematical modeling of in vitro dissolution data of optimised batch indicated the best fitting with Korsemeyer–Peppas model and the drug release kinetics primarily as fickian diffusion. All prepared solid dispersions showed dissolution improvement compared to pure drug. Almost similar dissolution profile was obtained as a function of storage time; this can be explained by no change in XRD and DSC patterns after 45 days of storage period. Keywords: Sirolimus, Gelucire®, Solid dispersion (SD), Adsorbent, Dissolution enhancement, Stability studies.

Improvement of dissolution rate of tacrolimus by solid dispersion technique

Tacrolimus has a poor solubility in water ranging from 4 to 12 μg mL−1. The mean bioavailability is ~21 %.The present study was carried out with a view to enhance the dissolution rate of poorly water-soluble drug tacrolimus using Gelucire 44/14® and Gelucire 50/13® as carriers and lactose monohydrate as an adsorbent. A combination of melt and adsorption techniques was employed for the preparation of solid dispersions (SD) to make final product easy for handling. Phase solubility study was conducted to evaluate the effect of carriers on aqueous solubility of tacrolimus. In order to elucidate the mechanism of dissolution enhancement, solid state characteristics were investigated using Fourier transform infrared spectroscopy, differential scanning calorimetry and powder X-ray diffraction. Mathematical modeling of in vitro dissolution data indicated the best fitting with Korsemeyer–Peppas model and the drug release kinetics primarily as Fickian/anomalous diffusion. All prepared solid dispersions showed dissolution improvement compared to pure drug, with Gelucire 50/13® as the superior carrier over Gelucire 44/14®. Almost similar dissolution profile was obtained as a function of storage time; this can be explained by no change in XRD and DSC pattern after 45 days storage period.