Liquisolid technique for dissolution rate enhancement of a high dose water-insoluble drug (carbamazepine)

Different liquisolid formulations of carbamazepine were accomplished by dissolving the drug in the non-toxic hydrophilic liquids, and adsorbing the solution onto the surface of silica. In order to reduce the amounts of carrier and aerosil in liquisolid formulations, some additives namely polyvinylpyrrolidone (PVP), hydroxypropyle methylcellulose (HPMC) and polyethylene glycol (PEG 35000) were added to liquid medication to increase loading factor. The effects of various ratios of carrier to coating material, PVP concentration, effect of aging and type of the carrier on dissolution rate of liquisolid compacts were studied. X-ray crystallography and differential scanning calorimetery (DSC) were used for evaluation of physicochemical properties of carbamazepine in liquisolid formulations. The results showed that the drug loading factor was increased significantly in the presence of additives. Liquisolid formulations containing PVP as additive, exhibited significantly higher drug dissolution rates compared to the compacts prepared by the direct compression technique. It was shown that microcrystalline cellulose had more liquid retention potential in comparison with lactose, and the formulations containing microcrystalline cellulose as carrier, showed higher dissolution rate. By decreasing the ratio of microcrystalline cellulose to silica from 20 to 10, an improvement in dissolution rate was observed. Further decrease in the ratio of microcrystalline cellulose:silica from 10 to 5 resulted in a significant reduction in dissolution rate. Increasing of PVP concentration in liquid medication caused a dramatic increase in dissolution rate at first 30min. The results showed that the dissolution rate of liquisolid tablets was not significantly affected by storing the tablets at 25 degrees C/75% relative humidity for a period of 6 months. The results of DSC and X-ray crystallography did not show any changes in crystallinity of the drug and interaction between carbamazepine and exipients during the process.     

Liquisolid Tablets for Dissolution Enhancement of a Hypolipidemic Drug

This investigation was aimed to improve the dissolution rate of the poorly soluble drug lovastatin, by formulating it as a liquisolid compact. Different liquisolid compacts were prepared using mathematical formulae to calculate the required quantities of powder and liquid ingredients to produce acceptably flowable and compressible admixture. Avicel PH 200, Cab-O-Sil, sodium starch glycolate and PEG 400 were employed as carrier, coating material, disintegrant and non-volatile liquid vehicle, respectively. The various drug to liquid and carrier to coating ratio were used to prepare liquisolid compacts. The formulated liquisolid tablets were evaluated for weight variation, hardness, drug content, friability and disintegration time. The in vitro release characteristics of the drug from tablets formulated by direct compression and liquisolid technique were compared in two different dissolution media. The tableting properties of the liquisolid compacts were within the acceptable limits and drug release rates were distinctly higher as compared to directly compressed tablets. The FTIR spectra showed no interaction between drug-excipient and disappearance of the characteristic absorption band of lovastatin in liquisolid formulations could be attributed to the formation of hydrogen bonding between the drug and liquid vehicle, which resulted in dissolution enhancement. Thus, the liquisolid technique was found to be a promising approach for improving the dissolution of a poorly soluble drug like lovastatin.     

Enhancement of dissolution rate of piroxicam using liquisolid compacts

Piroxicam is a poorly soluble, highly permeable drug and the rate of its oral absorption is often controlled by the dissolution rate in the gastrointestinal. The poor dissolution rate of water-insoluble drugs is still a major problem confronting the pharmaceutical industry. There are several techniques to enhance the dissolution of poorly soluble drugs. Among them, the technique of liquisolid compacts is a promising technique towards such a novel aim. In this study, the dissolution behaviour of piroxicam from liquisolid compacts was investigated in simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH 7.2). To this end, several liquisolid tablets formulations containing various ratios of drug:Tween 80 (ranging from 10% to 50% w/w) were prepared. The ratio of microcrystalline cellulose (carrier) to silica (coating powder material) was kept constant in all formulations. The results showed that liquisolid compacts demonstrated significantly higher drug release rates than those of conventionally made (capsules and directly compressed tablets containing micronized piroxicam). This was due to an increase in wetting properties and surface of drug available for dissolution.     

Liquisolid technique to enhance and to sustain griseofulvin dissolution: effect of choice of non-volatile liquid vehicles

Liquisolid systems were originally designed to enhance dissolution of hydrophobic drugs. Recently, the same technique was explored to control drug release via hydrophobic carriers. This work aimed to study the effects of different liquid vehicles on release characteristics of griseofulvin as a model hydrophobic drug. Fast dissolution tablets were prepared using three different non-ionic surfactants namely Cremophor(?)EL, Synperonic(?)PE/L61 and Capryol? 90, on the contrary Kollicoat(?)SR 30D was used for production of grieseofulvin sustained release formulations. Avicel(?) PH102 and Cab-O-Sil(?) M5 were used as carrier and coat materials, respectively. The effect of formulation parameters, such as drug concentration and carrier to coat ratio, on enhancing drug dissolution was explored. Drug concentrations of 20% and 40% (w/w), and R-values (carrier to coat ratio) of 10 and 20 were used. The mathematical model was utilized to formulate liquisolid powder systems. All fast release liquisolid formulations showed higher percentage drug dissolution efficiency (%DE) than conventional directly compacted tablets. Cremophor(?)EL showed the best dissolution enhancement with %DE of about 90%, compared to only 23% for conventional tablets; DSC data suggested loss of griseofulvin crystallinity and thermal behavior. Kollicoat(?) SR 30D retarded the drug release even in the presence of hydrophilic carrier; DSC data suggested that only small fraction of the drug was present in the molecular state within the system. The used liquisolid vehicles showed promise to enhance and to control (depend on the choice of the liquid vehicle) the release of griseofulvin from liquisolid compacts.     

Liquisolid systems to improve the dissolution of furosemide

A liquisolid system has the ability to improve the dissolution properties of poorly water soluble drugs. Liquisolid compacts are flowing and compactable powdered forms of liquid medications. The aim of this study was to enhance the in vitro dissolution properties of the practically water insoluble loop diuretic furosemide, by utilising liquisolid technique. Several liquisolid tablets were prepared using microcrystalline cellulose (Avicel® pH-101) and fumed silica (Cab-O-Sil® M-5) as the carrier and coating materials, respectively. Polyoxy-ethylene-polyoxypropylene-polyoxyethylene block copolymer (Synperonic® PE/L 81); 1,2,3-propanetriol, homopolymer, (9Z)-9-octadecenoate (Caprol® PGE-860) and polyethylene glycol 400 (PEG 400) were used as non- volatile water-miscible liquid vehicles. The liquid loading factors for such liquid vehicles were calculated to obtain the optimum amounts of carrier and coating materials necessary to produce acceptable flowing and compactible powder admixtures viable to produce compacts. The ratio of carrier to coating material was kept constant in all formulations at 20 to 1. The formulated liquisolid tablets were evaluated for post compaction parameters such as weight variation, hardness, drug content uniformity, percentage friability and disintegration time. The in-vitro release characteristics of the drug from tablets formulated by direct compression (as reference) and liquisolid technique, were studied in two different dissolution media. Differential scanning calorimetry (DSC) and Fourier-Transform infrared spectroscopy (FT-IR) were performed. The results showed that all formulations exhibited higher percentage of drug dissolved in water (pH 6.4–6.6) compared to that at acidic medium (pH 1.2). Liquisolid compacts containing Synperonic® PE/L 81 demonstrated higher release rate at the different pH values. Formulations with PEG 400 displayed lower drug release rate, compared to conventional and liquisolid tablets. DSC and FT-IR indicated a possible interaction between furosemide and tablet excipients that could explain the dissolution results. Caprol® PGE-860, as a liquid vehicle, failed to produce furosemide liquisolid compacts.     

Formulation and evaluation of liquisolid compacts of diclofenac sodium

The technique of liquisolid compacts is a promising method towards enhancing the dissolution of poorly soluble drugs. In the present study, the potential of liquisolid systems to improve the dissolution properties of water-insoluble agents was investigated using diclofenac sodium as the model drug. Several formulations of liquisolid compacts having different drug concentration (30% to 50% w/w) and with varying ratios of carrier to coat (i.e., different R values, ranging from 5 to 50) were prepared. Avicel and Aerosil were used as carrier and coat material, respectively, and propylene glycol was used as a nonvolatile liquid to prepare liquid medication. The effect of added liquid on the flowability and compressibility of the final admixture was studied and the effect of drug concentration on the dissolution pattern of diclofenac sodium was investigated. Liquisolid compacts demonstrated significantly higher drug release rates than the pure drug.     

Formulation factors affecting the release of ezetimibe from different liquisolid compacts

Context: Liquisolid technique is one of the methods used to improve the dissolution rate of the poorly water soluble drugs utilizing non volatile liquids.Objectives: Enhancement of the release of ezetimibe from different liquisolid formulations.Materials and Methods: Four liquid vehicles were used to prepare the liquid medications with different drug concentrations. The interaction between the drug and the excipients in liquisolid powders were characterized by DSC, X-ray, FTIR and SEM. Furthermore, the powder characteristics were evaluated by Carr’s Index and powder wetting time determinations, respectively. All prepared formulations were compressed at different pressures to end with the same constant porosity and the tablets were evaluated by different tests and compared with conventional formula. Results and Discussion: No interaction had been detected in all liquisolid formulations as shown in the results of XRD, FTIR, DSC and SEM. In addition to that, all liquisolid compacts had expressed faster dissolution profiles compared with that of conventional formula. Conclusion: The dissolution rate was affected by the drug concentration, solubility of the drug in the liquid vehicle and type of carrier. In addition, the presence of the liquid vehicle has been found to affect the mechanical properties of the liquisolid formulations.     

Effects of liquisolid formulations on dissolution of naproxen

The aim of this study was to investigate the use of liquisolid technique in improving the dissolution profiles of naproxen in a solid dosage form. This study was designed to evaluate the effects of different formulation variables, i.e. type of non-volatile liquid vehicles and drug concentrations, on drug dissolution rates. The liquisolid tablets were formulated with three different liquid vehicles, namely Cremophor^® EL (polyoxyl 35 castor oil), Synperonic^® PE/L61 (poloxamer 181, polyoxyethylene-polyoxypropylene copolymer) and poly ethylene glycol 400 (PEG400) at two drug concentrations, 20%w/w and 40%w/w. Avicel^® PH102 was used as a carrier material, Cab-o-sil^® M-5 as a coating material and maize starch as a disintegrant. The empirical method as introduced by Spireas and Bolton (1999) [1] was applied strictly to calculate the amounts of coating and carrier materials required to prepare naproxen liquisolid tablets. Quality control tests, i.e. uniformity of tablet weight, uniformity of drug content, tablet hardness, friability test, disintegration and dissolution tests were performed to evaluate each batch of prepared tablets. In vitro drug dissolution profiles of the liquisolid formulations were studied and compared with conventional formulation, in simulated gastric fluid (pH 1.2) and simulated intestinal fluid (pH 7.2) without enzyme. Stability studies were carried out to evaluate the stability of the tablets under humid conditions. Differential scanning calorimetry and Fourier transform infrared were used to investigate physicochemical interaction between naproxen and the excipients. It was found that liquisolid tablets formulated with Cremophor^® EL at drug concentration of 20%w/w produced high dissolution profile with acceptable tablet properties. The stability studies showed that the dissolution profiles of liquisolid tablets prepared with Cremophor^® EL were not affected by ageing significantly. Furthermore, DSC revealed that drug particles in liquisolid formulations were completely solubilised.     

Improvement of dissolution properties of Carbamazepine through application of the liquisolid tablet technique

The aim of the work was to improve the dissolution properties of the practically insoluble antiepileptic drug, Carbamazepine (CBZ) by adopting the liquisolid compaction technique. Reported liquid load factors, and excipient ratios were used to calculate the required amounts of excipients necessary to prepare the compacts or tablets according to a mathematical model. Avicel PH 102, and Aerosil 200 were used as the carrier and the coating materials, respectively, and explotab was used as disintegrant to prepare four tablet formulae, out of which formula 1 was successfully compressed into tablets. The dissolution patterns of liquisolid CBZ tablets, carried out according to the USP, were comparable to those of Tegretol^®. The protection of male albino mice against the convulsion, induced by electroshock, was lower in case of liquisolid tablets compared to Tegretol^® suspension and tablets probably due to the precipitation of CBZ in the silica pores resulting from its high dose.     

Formulation and optimization of liquisolid compact for enhancing dissolution properties of efavirenz by using DoE approach

Efavirenz displays low and variable bioavailability because of its poor aqueous solubility and high log P-value. The present investigation was aimed to improve the dissolution profile of efavirenz by using a simple, scalable and cost-effective technique of liquisolid compact. The drug was dissolved in Trancutol-HP for preparing the liquid medicament which was subsequently mixed with carrier and coating material to make free-flowing and compressible powder. 3² full factorial design was used to optimize the formulation in which the Neusilin US2/Corn starch ratios and carrier/coating material ratio were selected as independent variables. The results of in-vitro dissolution test proved that liquisolid compacts have significantly higher dissolution rate than tablets containing pure drug. Results of DSC and XRD studies suggested that the high dissolution of the drug from the liquisolid compacts was possibly because of the drug either being in an amorphous state or being molecularly dispersed within the internal matrix of compacts.     

Enhancement of famotidine dissolution rate through liquisolid tablets formulation: in vitro and in vivo evaluation

Although famotidine was reported to be 7.5 and 20 times more potent than ranitidine and cimetidine, respectively, its oral bioavailability is low and variable; due mainly to its poor aqueous solubility. The purpose of this study was to improve famotidine dissolution through its formulation into liquisolid systems and then to investigate the in vitro and in vivo performance of the prepared liquisolid tablets. The new mathematical model was utilized to formulate various liquisolid powder systems. Both DSC and XRD suggested loss of famotidine crystallinity upon liquisolid formulation which was further confirmed by SEM indicating that even though the drug existed in a solid dosage form, it is held within the powder substrate in a solubilized, almost molecularly dispersed state, which contributed to the enhanced drug dissolution properties. All the tested liquisolid tablet formulations showed higher drug dissolution rates (DR) than the conventional, directly compressed tables. In addition, the selected optimal formula released 78.36% of its content during the first 10 min which is 39% higher than that of the directly compressed tablets. Further, the bioavailability study indicated that the prepared optimal liquisolid formula did not differ significantly from the marketed famotidine tablets concerning Cmax, tmax, and AUC(0-8) at P<0.05.     

Use of the liquisolid compact technique for improvement of the dissolution rate of valsartan

The aim of this study was to improve the dissolution rate of the poorly soluble drug valsartan by delivering the drug as a liquisolid compact. Liquisolid compacts were prepared using propylene glycol as solvent, Avicel PH102 as carrier, and Aerosil 200 as the coating material. The crystallinity of the newly formulated drug and the interaction between excipients was examined by X-ray powder diffraction and Fourier-transform infrared spectroscopy, respectively. The dissolution studies for the liquisolid formulation and the marketed product were carried out at different pH values. The results showed no change in the crystallinity of the drug and no interaction between excipients. The dissolution efficiency of valsartan at 15 min was increased from 4.02% for plain drug and 13.58% for marketed product to 29.47% for the liquisolid formulation. The increase in the dissolution rate was also found to be significant compared to the marketed product at lower pH values, simulating the gastric environment where valsartan is largely absorbed. The liquisolid technique appears to be a promising approach for improving the dissolution of poorly soluble drugs like valsartan.     

Fabrication and characterization of liquisolid compacts of Embelin for dissolution enhancement

In the present investigation, an attempt was made to improve the dissolution properties of water insoluble herbal active ingredient, Embelin (EBN) by utilizing liquisolid technique, which might offer improved bioavailability. The compacts were prepared using Capryol 90 as non-volatile solvent, Neusilin as carrier and Aerosil 200 as coating material. Mathematical model and 3² factorial design with liquid load factor (X1) and drug concentration (X2) as the independent variables, was utilized to prepare the liquisolid powder systems. The prepared systems were subjected for studying micromeritic properties and possible drug-excipient interactions by fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). Dissolution studies revealed improvement in the drug release properties. Physicochemical characterization of liquisolid compacts by FTIR, DSC and PXRD techniques suggested reduction in drug crystallinity elaborating for the dissolution enhancement. The study reveals that liquisolid technique is a promising alternative for enhancing dissolution characteristics of EBN.     

Enhancement of griseofulvin release from liquisolid compacts

The potential of hydrophilic aerogel formulations and liquisolid systems to improve the release of poorly soluble drugs was investigated using griseofulvin as model drug. The in vitro release rates of this drug formulated as directly compressed tablets containing crystalline griseofulvin were compared to aerogel tablets with the drug adsorbed onto hydrophilic silica aerogel and to liquisolid compacts containing the drug dissolved or suspended in PEG 300. Furthermore, the commonly used carrier and coating materials in liquisolid systems Avicel® and Aerosil® were replaced by Neusilin®, an amorphous magnesium aluminometasilicate with an extremely high specific surface area of 339 m²/g to improve the liquisolid approach.Both the liquisolid compacts containing the drug dissolved in PEG 300 and the aerogel tablets showed a considerably faster drug release than the directly compressed tablets. With liquisolid compacts containing the drug suspended in PEG 300, the release rate increased with rising fraction of dissolved drug in the liquid portion. It could be shown that Neusilin® with its sevenfold higher liquid adsorption capacity than the commonly used Avicel® and Aerosil® allows the production of liquisolid formulations with lower tablet weights.     

Liquisolid technique: a promising alternative to conventional coating for improvement of drug photostability in solid dosage forms

Objective: The objective of this study was to investigate the photoprotective effect of liquisolid technique on amlodipine, a calcium channel blocker antihypertensive drug, representing a photosensitive drug model.

Method: Several liquisolid formulations were prepared using propylene glycol as a water-miscible nonvolatile vehicle at drug/solvent ratio (1:1), Avicel PH 102 as a carrier, nanometer-sized amorphous silicon and titanium dioxide either alone or in combination as coating materials. The carrier/coat ratio (R) was varied from 5 to 50. The prepared liquisolids, coated, noncoated tablets and drug substance were irradiated with a light dose of 0.5 W/m²/h visible light, 55.1 W/m²/h UVA, and 0.247 W/m²/h UVB for 8 h. The effect of coating material type and (R) value on the drug dissolution rate and photostability was studied. Results were statistically analyzed by post hoc two-way ANOVA at a probability level (α = 0.05).

Results: The results indicated that liquisolid technique not only improved the dissolution rate, but also significantly inhibited the photodegradative effect of different light energies in all prepared liquisolid formulations. The residual drug percentage reached 97.37% in comparison to 73.8% for the drug substance after 8 h of irradiation. The residual drug percentage was affected by the (R) value. Statistically; the detected difference was significant at the selected probability level (α = 0.05).

Conclusion: It can thus be concluded that this liquisolid technique is a promising alternative to conventional coating procedures in formulations containing photosensitive drugs.     

Investigation of the effect of solubility increase at the main absorption site on bioavailability of BCS class II drug (risperidone) using liquisolid technique

BCS class II drugs usually suffer inadequate bioavailability as dissolution step is the absorption rate limiting step. In this work, the effect of solubility increase at the main absorption site for these drugs was investigated using risperidone as a drug model. Liquisolid technique was applied to prepare risperidone per-oral tablets of high dissolution rate at intestinal pH (6.8) using versatile nonionic surfactants of high solubilizing ability [Transcutol HP, Labrasol and Labrasol/Labrafil (1:1) mixture] as liquid vehicles at different drug concentrations (10–30%) and fixed (R). The prepared liquisolid tablets were fully evaluated and the dissolution rate at pH 6.8 was investigated. The formulae that showed significantly different release rate were selected and subjected to mathematical modeling using DE₂₅, MDT and similarity factor (f2). Depending on mathematical modeling results, formula of higher dissolution rate was subjected to solid state characterization using differential scanning calorimetric (DSC), infrared spectroscopy (IR) and X-ray diffraction (XRD). Finally, the drug bioavailability was studied in comparison to conventional tablets in rabbits. Results showed that liquisolid tablet prepared using Labrasol/Labrafil (1:1) mixture as liquid vehicle containing 10% risperidone is a compatible formula with law drug crystallinity and higher dissolution rate (100% in 25?min). The drug bioavailability was significantly increased in comparison to the conventional tablets (1441.711?μg h/mL and 137.518?μg/mL in comparison to 321.011?μg h/mL and 38.673?μg/mL for AUC and Cp_max, respectively). This led to the conclusion that liquisolid technique was efficiently improved drug solubility and solubility increase of BCS class II drugs at their main absorption site significantly increases their bioavailability.     

Evaluation of Bioadhesive Glipizide Spheres and Compacts from Spheres Prepared by Extruder/Marumerizer Technique

The objective of this study was to attempt to deliver glipizide from spheres and compacts containing the natural polymer Carrageenan (Gelcarin, GP 812) and prepared by extruder/marumerizer technique. A second objective was to evaluate the mucoadhesive strength of the bioadhesive spheres onto the mucus membrane of rabbit. The effects of polymer, drug level, and type of spheronizing material were evaluated. All sphere formulations were compacted into tablets using a rotary Manesty B-3B machine equipped with 12/32 flat face tooling. Results show drug release from spheres and compacts decreased as the level of Carrageenan was increased. However, as the level of drug was increased drug release also increased. Spheres containing Avicel PH-101 gave higher drug release than spheres of the same composition but prepared with Avicel RC-581. In general, the drug release from tablets was higher than its corresponding spheres and drug release from spheres and tablets containing Carrageenan was higher than control spheres and tablets of the same composition but without Carrageenan. Tablet formulations compacted from spheres containing Avicel RC-581 gave higher release rate constants than tablet formulations of the same composition but prepared with Avicel PH-101. The bioadhesion study showed that mucoadhesion strength between spheres and mucus membrane of the rabbit depends on the levels of polymer, drug, and type of spheronizing material. Developed bioadhesive spheres and tablets increase the solubility of glipizide which may increase its bioavailability and also increased the adherence of the bioadhesive systems to the mucous membrane so that once daily dose can be administered.     

Evaluation of bioadhesive glipizide spheres and compacts from spheres prepared by extruder/marumerizer technique

The objective of this study was to attempt to deliver glipizide from spheres and compacts containing the natural polymer Carrageenan (Gelcarin, GP 812) and prepared by extruder/marumerizer technique. A second objective was to evaluate the mucoadhesive strength of the bioadhesive spheres onto the mucus membrane of rabbit. The effects of polymer, drug level, and type of spheronizing material were evaluated. All sphere formulations were compacted into tablets using a rotary Manesty B-3B machine equipped with 12/32 flat face tooling. Results show drug release from spheres and compacts decreased as the level of Carrageenan was increased. However as the level of drug was increased drug release also increased. Spheres containing Avicel PH-101 gave higher drug release than spheres of the same composition but prepared with Avicel RC-581. In general, the drug release from tablets was higher than its corresponding spheres and drug release from spheres and tablets containing Carrageenan was higher than control spheres and tablets of the same composition but without Carrageenan. Tablet formulations compacted from spheres containing Avicel RC-581 gave higher release rate constants than tablet formulations of the same composition but prepared with Avicel PH-101. The bioadhesion study showed that mucoadhesion strength between spheres and mucus membrane of the rabbit depends on the levels of polymer, drug, and type of spheronizing material. Developed bioadhesive spheres and tablets increase the solubility of glipizide which may increase its bioavailability and also increased the adherence of the bioadhesive systems to the mucous membrane so that once daily dose can be administered.     

Influence of cyclodextrin complexation on piroxicam gel formulations

The aim of this work was to evaluate the role of cyclodextrins in topical drug formulations. Solid piroxicam (PX) complexes with beta-cyclodextrin (beta-CD) and randomly methylated beta-cyclodextrin (RAMEB) were prepared by freeze-drying and characterized using differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), Fourier transform infrared spectroscopy (FTIR) and near infrared spectroscopy (NIR). A physical mixture of PX and cyclodextrins was characterized by enhanced dissolution properties compared to the dissolution profile of the pure drug due to in situ complex formation. Formation of the PX-cyclodextrin inclusion complex additionally improved the drug dissolution properties. Influence of CDs on drug permeation from the water dispersion and the prepared hydroxypropyl methylcellulose (HPMC) gels was investigated. Permeation of the drug involved three consecutive processes: dissolution of the solid phase, diffusion across the swollen polymer matrix and drug permeation through the membrane. Complexation increased PX diffusion by increasing the amount of diffusible species in the donor phase. Slower drug diffusion through the HPMC matrix was the rate limiting step in the overall diffusion process. Possible interaction between the hydrophilic polymer and cyclodextrin may result in physicochemical changes, especially in a change of rheological parameters.     

The dissolution enhancement of piroxicam in its physical mixtures and solid dispersion formulations using gluconolactone and glucosamine hydrochloride as potential carriers

Abstract

The solid dispersion technique is one of the most effective methods for improving the dissolution rate of poorly water-soluble drugs; however this is reliant on a suitable carrier and solvent being selected. The work presented explores amino sugars (d-glucosamine HCl and d-gluconolactone) as potential hydrophilic carriers to improve dissolution rate of a poorly water-soluble drug, piroxicam, from physical mixtures and solid dispersion formulations. Solid dispersions of the drug and carrier were prepared using different ratios by the conventional solvent evaporation method. Acetone was used as solvent in the preparation of solid dispersions. Physical mixtures of piroxicam and carrier were also prepared for comparison. The properties of all solid dispersions and physical mixtures were studied using a dissolution tester, Fourier transform infrared, XRD, SEM and differential scanning calorimetry. These results showed that the presence of glucosamine or gluconolactone can increase dissolution rate of piroxicam compared to pure piroxicam. Glucosamine or Gluconolactone could be used as carrier in solid dispersion formulations and physical mixtures to enhance the dissolution rate. Solid state studies showed that no significant changes occurred for piroxicam in physical mixtures and solid dispersion.