Evaluation of zidovudine encapsulated ethylcellulose microspheres prepared by water-in-oil-in-oil (w/o/o) double emulsion solvent diffusion technique

The preparation of zidovudine-loaded ethylcellulose microspheres by w/o/o double emulsion solvent diffusion method with high entrapment capacity and sustained release is described. A mixed solvent system (MSS) consisting of acetonitrile and dichloromethane in a 1:1 ratio and light liquid paraffin was selected as primary and secondary oil phases, respectively. Span 80 was used as the secondary surfactant for stabilizing the external oil phase. Spherical free flowing microspheres were obtained. The prepared microspheres were characterized by entrapment efficiency, in vitro release behavior, differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). The drug-loaded microspheres showed 32 - 55% entrapment capacity. The in vitro release profile could be altered significantly by changing various processing and formulation parameters to give sustained release of drug from the microspheres. The DSC thermograms confirmed the absence of any drug-polymer interaction. SEM studies showed that the microspheres were spherical and porous in nature. The in vitro release profiles from microspheres of different polymer-drug ratios were best fitted to Higuchi model with high correlation coefficient and the n value obtained from Korsmeyer-Peppas model was ranged between 0.23 - 0.54. The drug release was found to be diffusion controlled mechanism.     

Physicochemical characterization of solid dispersions of three antiepileptic drugs prepared by solvent evaporation method

We have investigated the solid dispersion and dissolution profiles of three antiepileptic drugs (carbamazepine (CBZ), oxcarbazepine (OXC) and rufinamide (RFN)) with different aqueous solubilities, prepared by the solvent evaporation method. Solid dispersions of the three drugs in hydroxy-propylmethylcellulose (HPMC), with drug:polymer ratios of 1:4, were prepared and characterized by differential scanning calorimetry (DSC), Fourier transformation infrared (FTIR) spectroscopy, X-ray diffraction (XRD) and scanning electron microscopy. The release mechanism was also investigated and the kinetic order of the solid dispersions was evaluated. It appeared that the dissolution behaviour depended on the physicochemical properties of the drug and drug-polymer interactions. DSC thermographs showed amorphous forms for all drugs confirmed by XRD patterns. The FTIR spectra of CBZ and OXC demonstrated drug interactions with HPMC through hydrogen polymer bonds. Thus, solid dispersions of these drugs had an improved dissolution profile. In contrast, solid dispersions of RUF showed modest enhancement of dissolution, suggesting negligible drug-polymer interactions. The different dissolution behaviour is attributed to the extent of interactions between the polymer hydroxyl group and the drug amide groups.     

Spray-dried chitosan/ethylcellulose microspheres for nasal drug delivery: swelling study and evaluation of in vitro drug release properties

The aim of this study was to develop spray-dried chitosan-based microspheres, suitable for nasal delivery of loratadine, and to evaluate their potential of modifying loratadine release. The microspheres were composed with ethylcellulose (EC) and chitosan (CM) in two different weight ratios, 1:2 and 1:3. One-phase systems (dispersions) and two-phase systems (emulsions and suspensions) were subjected to spray-drying, resulting in conventional and composed microspheres, respectively. The microspheres were evaluated with respect to the yield, particle size, encapsulation efficiency, physical state of the drug in the polymer matrix, swelling properties and in vitro drug release profile. It was shown that particle size, swelling ability and loratadine release from spray-dried microspheres were significantly affected by the polymeric composition and feed concentration in spray-drying process. Emulsifying method to produce composed EC/CM microspheres resulted in improved loratadine entrapment and moderate swelling, when compared to conventional chitosan microspheres. It seems like better formation of EC cores and chitosan coating were obtained when higher feed concentration and ultrasonic homogenization were employed in the preparation of emulsion systems and when EC to CM weight ratio was 1:3.     

Glutaraldehyde cross-linked chitosan microspheres for controlled delivery of zidovudine

Zidovudine-Chitosan microspheres were prepared by a suspension cross-linking method. The chitosan was dissolved in 2% acetic acid solution and this solution was dispersed in the light liquid paraffin. Span-80 was used as an emulsifier and glutaraldehyde as cross-linking agent. The prepared microspheres were slight yellow, free flowing and characterized by drug loading, infrared spectroscopy (IR), differential scanning colorimetry (DSC) and scanning electron microscopy (SEM). The in-vitro release studies are performed in pH 7.4 buffer solution. Microspheres produced are spherical and have smooth surfaces, with sizes ranging between 60-210 μm, as evidenced by SEM and particle size analysis. The drug loaded microspheres showed up to 60% of entrapment and release was extended up to 18-24 h. Among all the systems studied, the 35% Glutaraldehyde crosslinked, microspheres with 1 : 6 drug/chitosan ratio showed 75% release at 12 h. The infrared spectra and DSC thermograms showed stable character of zidovudine in the drug loaded microspheres and revealed the absence of drug-polymer interactions. Data obtained from in vitro release were fitted to various kinetic models and high correlation was obtained in the Higuchi model. The drug release was found to be diffusion controlled.     

Multiparticulate System for Colon Targeted Delivery of Ondansetron

Targeted delivery of drugs to colon has the potential for local treatment of a variety of colonic diseases. The main objective of the study was to develop a multiparticulate system containing chitosan microspheres for the colon targeted delivery of ondansetron for the treatment of irritable bowel syndrome. This work combines pH-dependent solubility of eudragit S-100 polymers and microbial degradability of chitosan polymers. Chitosan microspheres containing ondansetron were prepared by emulsion cross linking method. The effect of process variables like chitosan concentration, drug-polymer ratio, emulsifier concentration and stirring speed were studied on particle size and entrapment efficiency of chitosan microspheres. In vitro drug release studies in simulated gastro intestinal fluids showed a burst drug release pattern in the initial hour necessitating microencapsulation around the chitosan microspheres. The optimized formulation was then subjected to microencapsulation with eudragit S-100 by solvent evaporation technique. The effect of different coat/core ratio on particle size, drug entrapment efficiency and in vitro drug release were studied. Formulation which contain 1:10 core/coat ratio released lesser amount of drug in the upper gastro intestinal conditions and so selected as best formulation and then subjected to in vitro drug release studies in presence of rat ceacal contents to assess biodegradability of chitosan microspheres in colon. In order to study the drug release mechanism in vitro drug release data was fitted into various kinetic models. Analysis of regression values suggested that the possible drug release mechanism was Peppas model.     

Gemfibrozil encapsulation and release from microspheres and macromolecular conjugates

The purpose of this study was to evaluate and compare the ability of the macromolecular conjugates and microspheres to modify the release rate of gemfibrozil (Gem). Gem was covalently linked to two similar polymers: poly[alpha,beta-(N-2-hydroxyethyl-DL-aspartamide)] (PHEA) and poly[alpha,beta-(N-3-hydroxypropyl-DL-aspartamide)] (PHPA) by an ester linkage. The polymer-drug conjugates obtained (PHEA-G(1-3) and PHPA-G) differ in weight-average molecular weight, length of spacer and Gem content. Microspheres, composed of chitosans of different molecular weight alone or as a mixture with (2-hydroxypropyl)methylcellulose (HPMC), PHEA or PHPA and with different theoretical polymer/drug ratio (2:1 and 3:1, w/w) were prepared by spray drying. The microparticulate systems were morphologically characterised by scanning electron microscopy, particle size analysis and Gem content was determined. In vitro dissolution tests were performed to evaluate the feasibility of conjugates and microspheres in modulating Gem release. The results obtained show that microspheres are always suitable to modulate Gem release and that the best conditions are achieved by microspheres composed of the low molecular weight chitosan (CL) combined with PHPA or HPMC with either 2:1 or 3:1 (w/w) polymer/drug ratio. The PHEA-G conjugates exhibited rapid Gem release within less than 2 h, while the PHPA-G conjugate showed sustained Gem release profiles over a 10-h period.     

Development and characterization of mucoadhesive microspheres for nasal delivery of ketorolac

The objective of the present investigation was to prepare mucoadhesive microspheres of ketorolac for nasal administration by means of a solvent evaporation technique using carbopol (CP), polycarbophil (PL) and chitosan (CS) as mucoadhesive polymers. The prepared microspheres were characterized for morphology, swelling behavior, mucoadhesion, interaction studies, drug encapsulation efficiency, in vitro drug release, release kinetics, and ex vivo nasal cilio toxicity studies. The effects of various process variables on the particle size of the microspheres were investigated. Drug encapsulation efficiency and particle size of the microspheres ranged from 52-78% w/w and 14-46 microm respectively. Interaction studies revealed that there were no drug-polymer interactions. The in vitro release profiles showed prolonged-release of the drug. In vitro release data showed a good fit with the Higuchi model, and indicated Fickian diffusion. No severe damage was found to the integrity of nasal mucosa after ex vivo experiments.     

Study of processing parameters influencing the properties of diltiazem hydrochloride microspheres

Diltiazem hydrochloride-ethylcellulose microspheres were prepared by the water-in-oil emulsion-solvent evaporation technique. Small and spherical microspheres having a mean microsphere diameter in the range of 40-300 microm and entrapment efficiency of approximately 60-90% were obtained. Scanning electron micrographs of drug-loaded microspheres showed the presence of uniformly distributed small pores and absence of drug crystals on their surface, indicating simultaneous precipitation of drug and the polymer from the solvent during solvent evaporation. Differential scanning calorimetric analysis confirmed the absence of any drug-polymer interaction. The in vitro release profile could be altered significantly by changing various processing parameters to give a controlled release of drug from the microspheres. The stability studies of the drug-loaded microspheres showed that the drug was stable at storage temperatures, 5-55 degreesC, for 12 weeks.     

Formulation and in vitro evaluation of ethyl cellulose microspheres containing zidovudine

The aim of this study was to formulate and evaluate microencapsulated controlled release preparations of zidovudine using ethyl cellulose as the retardant material with high entrapment efficiency and extended release. Microspheres were prepared by water-in-oil-in-oil (w/o/o) double emulsion solvent diffusion method. A mixed solvent system (MSS) consisting of acetonitrile and dichloromethane in a 1:1 ratio and light liquid paraffin were chosen as primary and secondary oil phases, respectively. Span 80 was used as the surfactant for stabilizing the secondary oil phase. The prepared microspheres were white, free flowing and spherical in shape and characterized by drug loading, infrared spectroscopy (IR), differential scanning colorimetry (DSC) and scanning electron microscopy (SEM). The in vitro release studies were performed using PH 7.4 phosphate buffer. The drug loaded microspheres showed 41–55% of entrapment and release was extended up to 18–20?h. The infrared spectra and DSC and DTA thermograms showed stable character of zidovudine in the drug loaded microspheres and revealed the absence of drug-polymer interactions. SEM studies showed that the microspheres are spherical and porous in nature. Data obtained from in vitro release were fitted to various kinetic models and high correlation was obtained in the Higuchi model. The drug release was found to be diffusion controlled.     

Formulation and in vitro evaluation of ethyl cellulose microspheres containing zidovudine

The aim of this study was to formulate and evaluate microencapsulated controlled release preparations of zidovudine using ethyl cellulose as the retardant material with high entrapment efficiency and extended release. Microspheres were prepared by water-in-oil-in-oil (w/o/o) double emulsion solvent diffusion method. A mixed solvent system (MSS) consisting of acetonitrile and dichloromethane in a 1:1 ratio and light liquid paraffin were chosen as primary and secondary oil phases, respectively. Span 80 was used as the surfactant for stabilizing the secondary oil phase. The prepared microspheres were white, free flowing and spherical in shape and characterized by drug loading, infrared spectroscopy (IR), differential scanning colorimetry (DSC) and scanning electron microscopy (SEM). The in vitro release studies were performed using PH 7.4 phosphate buffer. The drug loaded microspheres showed 41-55% of entrapment and release was extended up to 18-20 h. The infrared spectra and DSC and DTA thermograms showed stable character of zidovudine in the drug loaded microspheres and revealed the absence of drug-polymer interactions. SEM studies showed that the microspheres are spherical and porous in nature. Data obtained from in vitro release were fitted to various kinetic models and high correlation was obtained in the Higuchi model. The drug release was found to be diffusion controlled.     

Preparation and characterization of chitosan-treated alginate microparticles incorporating all-trans retinoic acid

Chitosan treated alginate microparticles were prepared with the purpose of incorporating all-trans retinoic acid (ATRA) using an inexpensive, simple and fast method, enhancing dermal localization and sustaining the release of ATRA into the skin. Microparticles characterization, drug-polymer interaction, release profile and in vitro skin retention were investigated. Microparticles presented spherical shape and drug loading capacity of 47%. The drug content of these microparticles was affected by ATRA concentration and by the solvent used and it was more weakly affected by chitosan concentration. The release of ATRA was also affected by chitosan concentration. Microparticles prepared with 0.4% chitosan (w/w) resulted in drug release with a more sustained profile. The results of in vitro retention studies showed that chitosan treated alginate microparticles decreased the drug retention in the stratum corneum (SC), where occur the skin irritation, but maintained the ATRA concentration in the deeper skin layers, where occur the pathologies treated with ATRA. Then, the microparticles developed in this work can be a good candidate to improve the topical therapy with retinoid.     

Evaluation of furosemide-loaded alginate microspheres prepared by ionotropic external gelation technique

Alginate microspheres containing furosemide were prepared by the ionotropic external gelation technique using Ca2+, Al3+ and Ba2+ ions. The incorporation efficiency of the prepared microspheres ranged between 65% and 93%. The effect of sodium alginate concentration, cross-linking ions and drying conditions was evaluated with respect to entrapment efficiency, particle size, surface characteristics and in vitro release behavior. Infrared spectroscopic study confirmed the drug-polymer compatibility. Differential scanning calorimetric analysis revealed that the drug was molecularly dispersed in the alginate microsphere matrices. Scanning electron microscopic study of microspheres showed the rough surface due to higher concentration of drug molecules dispersed at molecular level in the alginate matrices. The mean particle size and entrapment efficiency were found to be varied by changing various formulation parameters. The in vitro release profile could be altered significantly by changing various formulation parameters to give a sustained release of drug from the microspheres. The kinetic modeling of the release data indicate that furosemide release from the alginate microspheres follow anomalous transport mechanism after an initial lag period when the drug release mechanism was found to be Fickian diffusion controlled.     

Preparation and in vitro evaluation of sustained release tablet formulations of diclofenac sodium

The effects of formulation variables on the release profile of diclofenac sodium (DS) from hydroxypropylmethyl cellulose (HPMC) and chitosan matrix tablets were studied. DS tablets were prepared by wet granulation and direct compression methods and different ratios of HPMC and chitosan were used. Physical properties of the prepared tablets and targeted commercial sustained release (SR) tablet and the drug release were studied in tablets that were placed in 0.1 M HCl for 1 h and phosphate buffer solution was added to reach pH value of 7.5. In vitro studies showed that 20% HPMC contained SR formulation with direct (dry) compression method is the optimum formulation due to its better targeting profile in terms of release. This formulation also exhibited the best-fitted formulation into the zero order kinetics. The precision and accuracy of the analytical method were also checked. The repeatability and reproducibility of the method were also determined.     

Study of processing parameters influencing the properties of Diltiazem hydrochloride microspheres

Diltiazem hydrochloride-ethylcellulose microspheres were prepared by the water-in-oil emulsion-solvent evaporation technique. Small and spherical microspheres having a mean microsphere diameter in the range of 40-300 µm and entrapment efficiency of ~60-90% were obtained. Scanning electron micrographs of drug-loaded microspheres showed the presence of uniformly distributed small pores and absence of drug crystals on their surface, indicating simultaneous precipitation of drug and the polymer from the solvent during solvent evaporation. Differential scanning calorimetric analysis confirmed the absence of any drug-polymer interaction. The in vitro release profile could be altered significantly by changing various processing parameters to give a controlled release of drug from the microspheres. The stability studies of the drug-loaded microspheres showed that the drug was stable at storage temperatures, 5-55°C, for 12 weeks.     

Design and Evaluation of Niacin Microspheres

Present study aims to prepare and evaluate niacin microspheres. Niacin-ethyl cellulose microspheres were prepared by water-in-oil-in-oil double emulsion solvent diffusion method. Spherical, free flowing microspheres having an entrapment efficiency of 72% were obtained. The effect of polymer-drug ratio, surfactant concentration for secondary emulsion process and stirring speed of emulsification process were evaluated with respect to entrapment efficiency, in vitro drug release behavior and particle size. FT-IR and DSC analyses confirmed the absence of drug-polymer interaction. The in vitro release profile could be altered significantly by changing various processing and formulation parameters to give a controlled release of drug from the microspheres. The percentage yield was 85%, particle size range was 405 to 560 μm. The drug release was controlled for 10 h. The in vitro release profiles from optimized formulations were applied on various kinetic models. The best fit with the highest correlation coefficient was observed in Higuchi model, indicating diffusion controlled principle. The in vitro release profiles of optimized formulation was studied and compared with commercially available niacin extended release formulation.     

Designing polymeric microparticulate drug delivery system for hydrophobic drug quercetin

The aim of this study was to investigate pharmaceutical potentialities of a polymeric microparticulate drug delivery system for modulating the drug profile of poorly water-soluble quercetin. In this research work two cost effective polymers sodium alginate and chitosan were used for entrapping the model drug quercetin through ionic cross linking method. In vitro drug release, swelling index, drug entrapment efficiency, Fourier Transforms Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), X-ray Diffraction (XRD) and Differential Scanning Calorimetric (DSC) studies were also done for physicochemical characterization of the formulations. Swelling index and drug release study were done at a pH of 1.2, 6.8 and 7.4 to evaluate the GI mimetic action which entails that the swelling and release of the all the Formulation1 (F1), Formulation2 (F2) and Formulation3 (F3) at pH 1.2 were minimal confirming the prevention of drug release in the acidic environment of stomach. Comparatively more sustained release was seen from the formulations F2 & F3 at pH 6.8 and pH 7.4 after 7 h of drug release profiling. Drug entrapment efficiency of the formulations shows in F1 (D:C:A = 2:5:30) was approximately 70% whereas the increase in chitosan concentration in F2 (D:C:A = 2:10:30) has shown an entrapment efficiency of 81%. But the comparative further increase of chitosan concentration in F3 (D:C:A = 2:15:30) has shown a entrapment of 80% which is not having any remarkable difference from F2. The FTIR analysis of drug, polymers and the formulations indicated the compatibility of the drug with the polymers. The smoothness of microspheres in F2 & F3 was confirmed by Scanning Electron Microscopy (SEM). However F1 microsphere has shown more irregular shape comparatively. The DSC studies indicated the absence of drug-polymer interaction in the microspheres. Our XRD studies have revealed that when pure drug exhibits crystalline structure with less dissolution profile, formulated microparticles can help us to obtain amorphous form of the same drug that is likely to have more dissolution property. The findings of the study suggest that the microsphere formulations were a promising carrier for quercetin delivery and can be considered as a favorable oral controlled release dosage form for hydrophobic drug quercetin.     

喷雾干燥法制备鼻用甲氨蝶呤壳聚糖微球及其特性的考察

目的以壳聚糖为载体材料,甲氨蝶呤为模型药物,制备鼻腔给药甲氨蝶呤壳聚糖微球。方法采用喷雾干燥法制备甲氨蝶呤壳聚糖微球;采用正交设计优化制备工艺,并对药物的包封率、收率、粒径以及释放行为进行考察。结果优化条件下所得微球粒径分布较为均匀,平均粒径为4.0~5.0μm,制成微球后药物可缓慢释放,符合鼻腔给药的要求。结论该方法适用于甲氨蝶呤壳聚糖微球的制备,壳聚糖是良好的鼻用制剂的载体材料,可用于制备脑部靶向鼻黏膜给药制剂。     

Eudragit RL100 based microspheres for ocular administration of azelastine hydrochloride

In the present study, potential of polymeric microspheres for treatment of allergic conjunctivitis was investigated. Azelastine hydrochloride loaded Eudragit RL100 microspheres were prepared by solvent evaporation technique. The change in drug-polymer ratio on the particle size, zeta potential, entrapment efficiency and in?vitro drug release was investigated. As Eudragit concentration ranged from 40 to 80?mg/ml the size range obtained was 4.18-7.36?μm with positive zeta potential. With the increase in drug polymer ratio, the entrapment efficiency was increased with maximum 14.56%. In?vitro release studies demonstrated prolonged release of the drug over the period of 6?hr. Scanning electron micrographs showed that microspheres were spherical with distinct solid dense structure. Fourier transform infrared and differential scanning calorimetry studies concluded slight change in peak intensities of drug in microspheres. In?vivo studies in rat model indicated that reduction in eosinophil count number was more pronounced in azelastine hydrochloride microspheres than marketed formulation, Azelast?.     

Preparation and in vitro dissolution profile of zidovudine loaded microspheres made of Eudragit RS 100, RL 100 and their combinations

The objective of present investigation was to evaluate the entrapment efficiency of the anti-HIV drug, zidovudine, using two Eudragit polymers of different permeability characteristics and to study the effect of this entrapment on the drug release properties. In order to increase the entrapment efficiency optimum concentration of polymer solutions were prepared in acetone using magnesium stearate as droplet stabilizer. The morphology of the microspheres was evaluated using a scanning electron microscope, which showed a spherical shape with smooth surface. The mean sphere diameter was between 1000-3000 microm and the entrapment efficiencies ranged from 56.4-87.1%. Polymers were used separately and in combination to prepare different microspheres. The prepared microspheres were studied for drug release behavior in phosphate buffer at pH 7.4, because the Eudragit polymers are independent of the pH of the dissolution medium. The release profiles and entrapment efficiencies depended strongly on the structure of the polymers used as wall materials. The release rate of zidovudine from Eudragit RS 100 microspheres was much lower than that from Eudragit RL 100 microspheres. Evaluation of release data reveals that release of zidovudine from Eudragit RL 100 microspheres followed the Higuchi rule, whereas Eudragit RS 100 microspheres exhibited an initial burst release, a lag period for entry of surrounding dissolution medium into polymer matrix and finally, diffusion of drug through the wall material.     

Chitosan and chondroitin microspheres for oral-administration controlled release of metoclopramide.

This study investigated the usefulness of chitosan and chondroitin sulphate microspheres for controlled release of metoclopramide hydrochloride in oral administration. Microspheres were prepared by spray drying of aqueous polymer dispersions containing the drug and different amounts of formaldehyde as cross-linker. Drug release kinetics were investigated in vitro in media of different pH. Chondroitin sulphate microspheres scarcely retarded drug release, regardless of cross-linker concentration and medium pH, and were thus not further characterized. Chitosan microspheres prepared with more than 15% formaldehyde (w/w with respect to polymer) showed good control release (more than 8 h), and release rates were little affected by medium pH. Release from chitosan microspheres prepared with 20% formaldehyde was independent of pH, suggesting that this may be the most appropriate formulation. The size distribution of the chitosan microparticles was clearly bimodal, with the smaller-diameter subpopulation corresponding to microsphere fragments and other particles. Electron microscopy showed the chitosan microspheres to be almost-spherical, though with shallow invaginations. The kinetics of drug release from chitosan microspheres were best fitted by models originally developed for systems in which release rate is largely governed by rate of diffusion through the matrix.