In Vitro Release Studies of Piroxicam from Oil-in-Water Creams and Hydroalcoholic Gel Topical Formulations

The importance of piroxicam, a therapeutic anti-inflammatory drug, is well known. Because of gastrointestinal disorders, dermatological dosage forms are recommended most. In our first studies, oil-in-water (O/W) creams of piroxicam (1% concentration) were prepared using glyceryl monostearate (GMS), stearic acid, and triethanolamine as additive ingredients. In our second studies, hydroalcoholic transparent gel formulations of this drug in a 0.5% concentration were prepared using hydroxypropylcellulose (HPC) as the gelling agent. The release of piroxicam from all formulations via dialysis through a cellulose membrane into phosphate buffer pH 6.8 at 37°C was studied. The effects of additives such as propylene glycol and 2-propanol on the drug release were also investigated. The release profiles from the standpoint of diffusion-controlled processes, as well as zero-order and first-order kinetics, were evaluated, and relevant parameters, such as diffusion coefficient, permeability coefficient, and partition coefficient, were calculated. The release obeys both the diffusion mechanism and first-order kinetics. The drug release from gel formulations containing 10%, 20%, and 30% propylene glycol was decreased due to the enhancement of viscosity. However, the limpidity of these formulations was improved. Moreover, the release of drug from gel formulations containing 15% and 20% of 2-propanol was increased. These results show that a hydroalcoholic gel formulation with HPC is a more suitable preparation of piroxicam when compared with an O/W cream formulation.     

Carboxymethyl Mungbean Starch as a New Pharmaceutical Gelling Agent for Topical Preparation

An application of carboxymethyl mungbean starch (CMMS) as a gelling agent in the topical pharmaceutical preparation was investigated. CMMS was prepared using specific conditions that yielded a high-viscosity product. Polymer gels and gel bases were prepared at 1–10% (wt/wt), and physicochemical studies were carried out in comparison with four standard gelling agents: carbopol 940 (CP), hydroxypropylmethyl cellulose (HPMC), methyl cellulose (MC), and sodium carboxymethyl cellulose (SCMC). Piroxicam was used as a model drug to study the drug release profile of the gel formulations. The tackless, greaseless, and transparent CMMS gels exhibited pseudoplastic behavior with thixotropy at concentrations less than 5% (wt/wt). At a concentration of 5% (wt/wt) and higher, the semisolid gels showed plastic flow characteristics. Viscosity and X-ray diffraction results indicated a good compatibility between CMMS and the acidic piroxicam. No precipitation of piroxicam or phase separation was observed during a stability test. The release rate of piroxicam from 3% (wt/wt) CMMS gel was 1,003.79 ± 105.08 μg/cm², which was comparable with 947.66 ± 133.70 μg/cm² obtained from a 0.5% (wt/wt) carbopol formulation. The release profiles of both formulations were consistent and remained unchanged after 2 months' storage. Viscosity played an important role in controlling the release rate of low concentration CMMS formulations by regulating the drug diffusion. At a concentration of 5% (wt/wt) CMMS and higher, the release rates of piroxicam were not significantly different. A plausible explanation based on the nature of the gelling agent was proposed. Stability and drug release profiles of CMMS and commercial gelling agents were compared. The results supported the potential use of CMMS as a new, effective gelling agent for topical gel preparation.     

Carboxymethyl mungbean starch as a new pharmaceutical gelling agent for topical preparation

An application of carboxymethyl mungbean starch (CMMS) as a gelling agent in the topical pharmaceutical preparation was investigated. CMMS was prepared using specific conditions that yielded a high-viscosity product. Polymer gels and gel bases were prepared at 1-10% (wt/wt), and physicochemical studies were carried out in comparison with four standard gelling agents: carbopol 940 (CP), hydroxypropylmethyl cellulose (HPMC), methyl cellulose (MC), and sodium carboxymethyl cellulose (SCMC). Piroxicam was used as a model drug to study the drug release profile of the gel formulations. The tackless, greaseless, and transparent CMMS gels exhibited pseudoplastic behavior with thixotropy at concentrations less than 5% (wt/wt). At a concentration of 5% (wt/wt) and higher, the semisolid gels showed plastic flow characteristics. Viscosity and X-ray diffraction results indicated a good compatibility between CMMS and the acidic piroxicam. No precipitation of piroxicam or phase separation was observed during a stability test. The release rate of piroxicam from 3% (wt/wt) CMMS gel was 1,003.79 +/- 105.08 microg/cm(2), which was comparable with 947.66 +/- 133.70 microg/cm(2) obtained from a 0.5% (wt/wt) carbopol formulation. The release profiles of both formulations were consistent and remained unchanged after 2 months' storage. Viscosity played an important role in controlling the release rate of low concentration CMMS formulations by regulating the drug diffusion. At a concentration of 5% (wt/wt) CMMS and higher, the release rates of piroxicam were not significantly different. A plausible explanation based on the nature of the gelling agent was proposed. Stability and drug release profiles of CMMS and commercial gelling agents were compared. The results supported the potential use of CMMS as a new, effective gelling agent for topical gel preparation.     

In vitro release and diffusion studies of promethazine hydrochloride from polymeric dermatological bases using cellulose membrane and hairless mouse skin

The study was designed to investigate the feasibility of developing a transdermal drug dosage form of promethazine hydrochloride (PMH). The in vitro release and diffusion characteristics of PMH from various dermatological polymeric bases were studied using cellulose membrane and hairless mouse skin as the diffusion barriers. These included polyethylene glycol (PEG), hydroxypropyl methylcellulose (HPMC), cross-linked microcrystalline cellulose, and carboxyl methyl cellulose sodium (Avicel CL-611), and a modified hydrophilic ointment USP. In addition, the effects of several additive ingredients known to enhance the drug release from topical formulations were evaluated. The general rank order for the drug release from these formulations using cellulose membrane was observed to be PEG > HMPC > Avicel CL-611 > hydrophilic ointment base. The inclusion of the additives had little or no effect on the drug diffusion from these bases, except for the hydrophilic ointment formulation containing 15% ethanol, which provided a significant increase in the drug release. However, when these formulations were studied for drug diffusion through the hairless mouse skin, the Avicel CL-611 base containing 15% ethanol exhibited the optimum drug release. The data also revealed that this formulation gave the highest steady-state flux, diffusion, and permeability coefficient values and correlated well with the amount of drug release.     

In Vitro Release and Diffusion Studies of Promethazine Hydrochloride from Polymeric Dermatological Bases Using Cellulose Membrane and Hairless Mouse Skin

The study was designed to investigate the feasibility of developing a transdermal drug dosage form of promethazine hydrochloride (PMH). The in vitro release and diffusion characteristics of PMH from various dermatological polymeric bases were studied using cellulose membrane and hairless mouse skin as the diffusion barriers. These included polyethylene glycol (PEG), hydroxypropyl methylcellulose (HPMC), cross-linked microcrystalline cellulose, and carboxyl methyl cellulose sodium (Avicel® CL-611), and a modified hydrophilic ointment USP. In addition, the effects of several additive ingredients known to enhance the drug release from topical formulations were evaluated. The general rank order for the drug release from these formulations using cellulose membrane was observed to be PEG > HMPC > Avicel CL-611 > hydrophilic ointment base. The inclusion of the additives had little or no effect on the drug diffusion from these bases, except for the hydrophilic ointment formulation containing 15% ethanol, which provided a significant increase in the drug release. However, when these formulations were studied for drug diffusion through the hairless mouse skin, the Avicel CL-611 base containing 15% ethanol exhibited the optimum drug release. The data also revealed that this formulation gave the highest steady-state flux, diffusion, and permeability coefficient values and correlated well with the amount of drug release.     

Piroxicam Release from Dermatological Base: In-Vitro Studies using Cellulose Membrane and Hairless Mouse Skin

Abstract

Piroxicam is one of the most potent non-steroidal, anti-inflammatory agents which also exhibits antipyretic activity. Piroxicam is well absorbed following the oral administration, however, its use has been associated with a number of gastro-intestinal disorders including bleeding and ulceration. To overcome these side effects, this study was undertaken to develop diadermatic dosage form using various polymeric gel and ointment bases containing 1% piroxicam were prepared to study the in-vitro release of the drug. Also, a series of additive ingredients, such as, alcohol USP, polyethylene glycol-400 and dimethyl sulfoxide (DMSO) were incorporated in these formulations at various concentration levels to evaluate their effects on drug release. The general rank order for the in-vitro drug release from all the bases evaluated was: gel base > hydrophillic base > emulsion base. In general, additives had little or no effect in enhancing the drug release from these bases. The in-vitro release data were treated with various kinetic principles to assess the relevant parameters, such as, diffusion coefficient, permeability coefficient, partition coefficient, zero order and first order rate constants. Among the formulations evaluated, the gel base containing (DMSO) gave the best in-vitro drug release both through the cellulose membrane and the hairless mouse skin.     

Evaluation of intratympanic formulations for inner ear delivery: methodology and sustained release formulation testing

A convenient and efficient in vitro diffusion cell method to evaluate formulations for inner ear delivery via the intratympanic route is currently not available. The existing in vitro diffusion cell systems commonly used to evaluate drug formulations do not resemble the physical dimensions of the middle ear and round window membrane. The objectives of this study were to examine a modified in vitro diffusion cell system of a small diffusion area for studying sustained release formulations in inner ear drug delivery and to identify a formulation for sustained drug delivery to the inner ear. Four formulations and a control were examined in this study using cidofovir as the model drug. Drug release from the formulations in the modified diffusion cell system was slower than that in the conventional diffusion cell system due to the decrease in the diffusion surface area of the modified diffusion cell system. The modified diffusion cell system was able to show different drug release behaviors among the formulations and allowed formulation evaluation better than the conventional diffusion cell system. Among the formulations investigated, poly(lactic-co-glycolic acid)–poly(ethylene glycol)–poly(lactic-co-glycolic acid) triblock copolymer systems provided the longest sustained drug delivery, probably due to their rigid gel structures and/or polymer-to-cidofovir interactions.     

Formulation study of topically applied O/W lotion containing vitamin D3 derivative, focusing on skin permeability of the drug

Permeation of 22-oxacalcitriol-1α, 25-dihydroxyvitamin D(3) (OCT) through excited hairless mouse skin was determined after application of OCT as solutions and O/W lotions consisted of different polarities of solvents: medium-chain fatty acid triglyceride (MCT), myristate isopropyl (IPM), 1,3-butylene glycol (1,3-BG), and propylene glycol (PG). OCT concentration in skin was also followed after applying these formulations. A two-layer diffusion model was composed to analyze dermatopharmacokinetic profiles of OCT for each vehicle. In the OCT solutions, skin permeation profile of OCT differed depending on solvent polarity. The O/W lotion with a high MCT content led to a low amount of OCT in skin. On the other hand, the O/W lotion with a high 1,3-BG content led to a high amount of OCT in skin. This dermatopharmacokinetic analysis indicated that addition of MCT to the formulation decreases the skin/vehicle partition coefficient of OCT and increases the diffusion coefficient of OCT in skin. However, the opposite effects on these two parameters were found in the case of 1,3-BG. Thus, skin permeability of OCT differed depending on the solvents used in the formulation. These results indicate that skin permeability of OCT is influenced by the physicochemical properties (i.e. polarity) of OCT, solvent, and skin. Our findings on the solvent effects of the skin permeability of OCT are thus useful for designing topical drug formulation, especially in aiming for bioequivalent dosage formulas.     

Permeation of piroxicam from the poloxamer gels

Topical formulations of piroxicam were prepared using poloxamer 407 or poloxamer 188 by a cold method, and the permeation characteristics of piroxicam were evaluated. The permeation rate of piroxicam across the synthetic cellulose membrane and the rat skin decreased as the concentration of poloxamer increased. Though poloxamer gel exhibits reversed thermal behavior, the permeation rate of piroxicam increased with increasing temperature, indicating that the diffusional pathway of piroxicam is a water channel within the gel formulation. The pH of the gel did not affect the permeation rate of piroxicam significantly. As the concentration of piroxicam in the gel formulation increased, the permeation rate of piroxicam increased up to 1% and reached a plateau above 1%. Among various enhancers tested, polyoxyethylene-2-oleyl ether showed the highest enhancing effect, with an enhancement ratio of 2.84. Based on experimental results, the permeation rate of piroxicam can be controlled by changing the poloxamer concentration or drug concentration and by the addition of an appropriate enhancer.     

In-Vitro Release Studies of Chlorpheniramine Maleate from Topical Bases Using Cellulose Membrane and Hairless Mouse Skin

Abstract

In-vitro release of chlorpheniramine maleate from various dermatological bases including a polymeric gel base, the modified hydrophilic base and the modified hydrophilic petrolatum base, was studied. The additive ingredients known to enhance the drug release from the topical bases were also evaluated at different concentration levels. These included urea, ethanol and dimethylsulfoxide (DMSO). The rank order of drug release through the cellulose membrane was observed to be: the gel base > the modified hydrophilic base > the modified hydrophilic petrolatum base. In general, the presence of the additives adversely affected the drug release except for the (DMSO) and ethanol in certain cases.

The formulations with optimum in-vitro release profiles of the drug through the cellulose membrane, were selected for further studies of the drug release using hairless mouse skin as the diffusion barrier. Here again, the gel formulation gave the best in-vitro release of the drug, and the data correlated well with the results previously obtained from the cellulose membrane.

The in-vitro data were treated with various kinetic principles to determine the relevant parameters, such as the steady state flux, the diffusion coefficient and the permeability coefficient. Using these information, the formulations were evaluated for their suitability for delivering chlorpheniramine maleate via the diadermatic dosage form.     

In vitro release studies of flurbiprofen from different topical formulations

The release profiles of flurbiprofen (F) from different gel and ointment formulations were studied in order to evaluate factors governing the release process. Carbopol 934P (CAB), poloxamer 407 (POL), and eudragit S100 (EUD) gel bases were used, while emulsion (EML) and polyethylene glycol (PEG) ointments were employed. The release studies were conducted using membraneless diffusion cells and lipophilic receptor medium, isopropyl myristate (IPM). The effects of gelling agent concentrations and the initial drug load on drug release were determined. Hydrogels were observed to give higher amounts of drug release than hydrophobic EUD gel and ointments, despite the lower bulk viscosity of these bases. Flurbiprofen release from CAB gels was 3.06-1.56-fold higher than from other formulations. Over a 4-hr period, the amount of F released was 492.8 and 316.0 µg/cm² from 2% CAB and 25% POL gels, while it was 213.05, 168.61, and 160.9 µg/cm² from EML, 40% EUD, and PEG bases, respectively. The diffusivity of F in the gel bases was an inverse function of the polymer concentrations over the range of 1-3% CAB, 20-30% POL, and 35-45% EUD gels. Drug release was increased from the bases as the initial F concentration increased over the range 0.25-1.0%, while the diffusion coefficient observed an inverse relationship. The CAB and POL gels could be the vehicles of choice for the rapid release and onset of F after topical application.     

The Stability of Theophylline Tablets with a Hydroxypropylcellulose Matrix

The behavior of 40:60 anhydrous theophylline/hydroxypropylcellulose (HPC) direct compression tablets obtained using a variety of hydroxypropylcelluloses with low or medium-high degrees of substitution (L-HPCs and HPCs, respectively) was determined immediately following their preparation and after storage for 6 months at 20°C and a relative humidity (RH) of either 70.4% or 93.9%. The lower relative humidity did not bring about hydration of the active principle in any formulation, but the higher relative humidity totally hydrated the drug in all except one L-HPC formulation, in which hydration remained incomplete. Both relative humidities caused significant tablet swelling, with L-HPC formulations being more affected than HPC formulations. Drug release was slowed by hydration of the active principle, but accelerated with tablet swelling. The lower relative humidity caused significant alteration of drug release characteristics in only two L-HPC formulations, release from which was accelerated, while the higher relative humidities only failed to cause such alterations in two HPC formulations, with release from all except one of the others slowed (in the exceptional formulation, which exhibited incompletely hydrated theophylline and the greatest swelling of all, release was accelerated).     

The stability of theophylline tablets with a hydroxypropylcellulose matrix

The behavior of 40:60 anhydrous theophylline/hydroxypropylcellulose (HPC) direct compression tablets obtained using a variety of hydroxypropylcelluloses with low or medium-high degrees of substitution (L-HPCs and HPCs, respectively) was determined immediately following their preparation and after storage for 6 months at 20°C and a relative humidity (RH) of either 70.4% or 93.9%. The lower relative humidity did not bring about hydration of the active principle in any formulation, but the higher relative humidity totally hydrated the drug in all except one L-HPC formulation, in which hydration remained incomplete. Both relative humidities caused significant tablet swelling, with L-HPC formulations being more affected than HPC formulations. Drug release was slowed by hydration of the active principle, but accelerated with tablet swelling. The lower relative humidity caused significant alteration of drug release characteristics in only two L-HPC formulations, release from which was accelerated, while the higher relative humidities only failed to cause such alterations in two HPC formulations, with release from all except one of the others slowed (in the exceptional formulation, which exhibited incompletely hydrated theophylline and the greatest swelling of all, release was accelerated).     

Topical permeation characteristics of diclofenac sodium from NaCMC gels in comparison with conventional gel formulations.

Topical gel formulations of diclofenac sodium were prepared by using sodium carboxymethylcellulose (NaCMC), a low-toxicity cellulose polymer as a gel-forming material that is biocompatible and biodegradable. The influence of various formulation variables, such as initial drug concentrations and NaCMC concentration, and certain skin permeation enhancers on release characteristics of the diclofenac sodium from the prepared gels through a standard cellophane membrane was studied in comparison with four commercially available gel formulations of diclofenac sodium,. The cumulative amounts released and the apparent release rates were higher for the prepared gels in comparison with the commercial formulations. Skin permeation studies using abdominal rat skin revealed good improvement of skin permeation characteristics of diclofenac sodium using NaCMC gels as compared to the commercial gels. The cumulative amount permeated at 6 h (microg/cm2), steady-state flux Jss (microg/cm2 h), lag time tL (h), permeability coefficient kp (cm/s), partition coefficient k, and diffusion coefficient D (cm2/s) were determined for the prepared gels in comparison with the commercial gels. Skin permeation enhancers such as isopropyl alcohol (IPA), Tween 80, and alpha-tocopherol polyethylene glycol succinate (TPGS) exhibited little or no effect on the permeation characteristics of diclofenac sodium. Infrared (IR) spectrum and differential scanning calorimetry (DSC) studies on the pure diclofenac sodium, NaCMC, and their physical mixture at a 1:1 ratio revealed that there was no positive evidence for the interactions between the drug and NaCMC, indicating the compatibility of the drug and the vehicle. Based on experimental results, preparation of diclofenac sodium gels using NaCMC vehicle is promising.     

5-Fluorouracil-loaded PLA/PLGA PEG–PPG–PEG polymeric nanoparticles: formulation,in vitro characterization and cell culture studies

In this study, 5-FU, a potent anticancer drug, is planned to be delivered via a new and promising drug delivery system, nanoparticles formed with hydrophobic core polymer and triblock copolymers; Poly(DL-lactic acid), Poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) copolymer (PLA/PEG-PPG-PEG) and Poly(D,L-lactide–co-glycolide)/Poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) copolymer (PLGA/PEG-PPG-PEG) nanoparticles. Particle size range of nanoparticles was found to be between 145 and 198?nm, which would promote the passive targeting of the nanoparticles to tumor cells based on the enhanced permeability and retention (EPR) effect. SEM images revealed all nanoparticles formulations to be spherical and without pores. Zeta potential, yield value and encapsulation efficiencies of 5-FU-loaded nanoparticles were within the range of ?11.1 and ?13.7?mV, 72.7–87.7% and 83.6–93.9%, respectively. Cumulative release of 5-FU was observed between 90% and 94.4% in all nanoparticle formulations by the end of 72?h, and fitness of release profiles to Higuchi model indicated matrix-controlled diffusion of the 5-FU from polymeric nanoparticles. Cell viability values of the cells treated with 5-FU-loaded nanoparticles were obtained as low as 47% and 52% with tetrazolium dye assay, suggesting that delivery of 5-FU via amphiphilic triblock copolymer nanoparticles would be a promising delivery system because of the EPR effect.     

Ketoconazole‐conjugated ZnO nanoparticles based semi‐solid formulation and study their impacts on skin disease

In this study, the ketoconazole‐conjugated zinc oxide (ZnO) nanoparticles were prepared in a single‐step approach using dextrose as an intermediate compound. The physical parameters confirmed the drug conjugation with ZnO and their size was around 70–75 nm. The drug loading and in vivo drug release studies indicated that the –CHO group from the dextrose increase the drug loading up to 65% and their release kinetics were also studied. The anti‐fungal studies indicated that the prepared nanoparticles exhibit strong anti‐fungal activity and the minimum concentration needed is 10 mg/ml. The nanoparticles loaded semi‐solid gel was prepared using carbopol, methylparaben, propyl paraben and propylene glycol. The in vitro penetration of the ketoconazole‐conjugated nanoparticles was studied using the skin. The results indicated that the semi‐solid gel preparations influenced the penetration and also favoured the accumulation into the skin membrane. The veterinary clinical studies indicated that the prepared gel is highly suitable for treatment of Malassezia.Inspec keywords: II‐VI semiconductors, skin, biomedical materials, antibacterial activity, wide band gap semiconductors, drug delivery systems, nanomedicine, drugs, diseases, gels, nanofabrication, nanoparticles, zinc compounds, biomembranes, veterinary medicineOther keywords: strong anti‐fungal activity, propyl paraben, propylene glycol, semisolid gel preparations, skin membrane, veterinary clinical studies, semisolid formulation, skin disease, ketoconazole‐conjugated zinc oxide nanoparticles, single‐step approach, physical parameters, drug conjugation, drug loading, release kinetics, dextrose, in vivo drug release studies, carbopol, methylparaben, in vitro penetration, Malassezia, ZnO     

In Vitro Release Studies of Flurbiprofen from Different Topical Formulations

ABSTRACT

The release profiles of flurbiprofen (F) from different gel and ointment formulations were studied in order to evaluate factors governing the release process. Carbopol 934P (CAB), poloxamer 407 (POL), and eudragit S100 (EUD) gel bases were used, while emulsion (EML) and polyethylene glycol (PEG) ointments were employed. The release studies were conducted using membraneless diffusion cells and lipophilic receptor medium, isopropyl myristate (IPM). The effects of gelling agent concentrations and the initial drug load on drug release were determined. Hydrogels were observed to give higher amounts of drug release than hydrophobic EUD gel and ointments, despite the lower bulk viscosity of these bases. Flurbiprofen release from CAB gels was 3.06–1.56-fold higher than from other formulations. Over a 4-hr period, the amount of F released was 492.8 and 316.0 µg/cm² from 2% CAB and 25% POL gels, while it was 213.05, 168.61, and 160.9 µg/cm² from EML, 40% EUD, and PEG bases, respectively. The diffusivity of F in the gel bases was an inverse function of the polymer concentrations over the range of 1–3% CAB, 20–30% POL, and 35–45% EUD gels. Drug release was increased from the bases as the initial F concentration increased over the range 0.25–1.0%, while the diffusion coefficient observed an inverse relationship. The CAB and POL gels could be the vehicles of choice for the rapid release and onset of F after topical application.     

Development and Optimization of a Methotrexate Topical Formulation

A topical methotrexate (MTX) formulation that would achieve optimal drug buildup in the epidermis and diminish potential systemic toxicity could be of great utility in the treatment of a variety of hyperproliferative skin disorders. In an attempt to develop an optimized MTX topical formulation containing pharmaceutically acceptable excipients, a 2³ factorial design was used to investigate the effects of a fatty alcohol, propylene glycol, and ethanol on the in vitro skin permeation and uptake of MTX. In vitro skin permeation studies were performed using excised human epidermis mounted in flow-through diffusion cells. The results of steady-state flux and skin uptake of MTX from these formulations ranged from 0.035 to 0.315 μg/cm²/hr and 1.146 to 7.929 μg/cm², respectively. Response surface analysis was used to determine the optimum formulation in terms of skin permeation and uptake of MTX.

An optimized cream formulation was developed and compared to a gel formulation containing 3% Azone in hairless mice to evaluate the uptake of MTX in the treated and untreated skin sites as well as the distribution of MTX in the blood and liver following topical application. The results of the in vivo study demonstrated the localization of MTX at the treated site for both formulations without significant uptake of MTX in the distant untreated epidermis and dermis. The levels of MTX in the blood and liver following topical application of the optimized cream were significantly less than those of the gel formulation with 3% Azone.     

Formulation development of allopurinol suppositories and injectables

Allopurinol was formulated into injectable and suppository dosage forms. The injectable formulation was prepared by dissolving allopurinol in a cosolvent system consisting of dimethyl sulfoxide (DMSO) and propylene glycol (v/v = 50/50). The stability of allopurinol in the cosolvent system was studied under accelerated storage conditions, and results indicate first-order degradation kinetics with an activation energy of 24.3 kcal/mol. The development of suppository dosage forms was performed by formulating allopurinol with polyethylene glycol (PEG) mixtures of different molecular weights. In vitro release profiles of suppositories formulated with different polyethylene bases were obtained in the pH 7.4 buffer solution using the USP 23 paddle method at 100 rpm. Results indicate that the release rate of the suppository formulations containing PEG 1500/PEG 4000 at the ratio (w/w) of 2.5/10 to 10/2.5 appeared to be similar. However, the addition of sodium lauryl sulfate in the suppository decreased the release rate of allopurinol significantly. A future study to establish in vitro/in vivo correlation (iv/ivc) is suggested.     

In vitro release of ketoprofen from hydrophilic matrix tablets containing cellulose polymer mixtures

The effect of cellulose ether polymer mixtures, containing both hydroxypropylcellulose (HPC) and hydroxypropylmethylcellulose (HPMC K15M or K100M), on ketoprofen (KTP) release from matrix tablets was investigated. In order to evaluate the compatibility between the matrix components, Raman spectroscopy, scanning electron microscopy (SEM), and X-ray powder diffraction (XRPD) experiments were performed. The results evidence the absence of significant intermolecular interactions that could eventually lead to an incompatibility between the drug and the different excipients. Formulations containing mixtures of polymers with both low and high viscosity grades were prepared by a direct compression method, by varying the polymer/polymer (w/w) ratio while keeping the drug amount incorporated in the solid dispersion constant (200?mg). The hardness values of different matrices were found within the range 113.8 to 154.9 N. HPLC analysis showed a drug content recovery between 99.3 and 102.1%, indicating that no KTP degradation occurred during the preparation process. All formulations attained a high hydration degree after the first hour, which is essential to allow the gel layer formation prior to tablet dissolution. Independent-model dissolution parameters such as t_10% and t_50% dissolution times, dissolution efficiency (DE), mean dissolution time (MDT), and area under curve (AUC) were calculated for all formulations. Zero-order, first-order, Higuchi, and Korsmeyer–Peppas kinetic models were employed to interpret the dissolution profiles: a predominantly Fickian diffusion release mechanism was obtained – with Korsmeyer–Peppas exponent values ranging from 0.216 to 0.555. The incorporation of HPC was thus found to play an essential role as a release modifier from HPMC containing tablets.