Studies on the in vitro Release of Ibuprofen from Polyethylene Glycol-Polyvinyl Acetate Mixtures Liquid Filled into Hard Gelatin Capsules

The release of ibuprofen from mixtures of polyethylene glycol (PEG) with polyvinyl acetate (PVAc) has been studied in vitro and complemented by x-ray diffraction measurements, differential scanning calorimetry (DSC), and melting point determinations via hot-stage microscopy (HSM). Results indicate that ibuprofen release can be affected markedly by alteration of the PVAc concentration. The molecular weight of the PEG and the pH of the dissolution medium are also shown to affect the release profile. Visual observation during the drug release process revealed a complex behavior which included emission of liquidlike droplets, formation of a crust around the releasing mass, and/or production of flakes of solid material. This behavior appeared to have a disadvantageous effect on the reproducibility of drug release. Construction of a phase diagram from results of thermal analysis using DSC and HSM indicated the formation of an eutectic mixture with a composition of 35% ibuprofen and 65% PEG 1500 and a melting point of 36°C. The complex behavior of the drug-releasing mass is discussed in terms of this phase diagram. Only the release data for systems containing 4% w/w or more of PVAc could be linearized by plotting against the square root of time whereas data for all of the systems studied could be linearized by first-order plots.     

An approach to controlled-release dosage form of propranolol hydrochloride

It is possible to release a drug with only limited diffusion from a membrane-coated system using osmotic pumping. In this study, a propranolol osmotic pump was produced by coating the core tablets with cellulose acetate. The effects of membrane thickness, pore size, and stirring rate on the release rate of propranolol hydrochloride were studied. It was found that the thickness of cellulose acetate membrane had a profound effect on the release rate of propranolol hydrochloride from the membrane-coated tablets. The results showed that, when the membrane thickness increased, the release rate of propranolol decreased. The drug release follows a zero-order release when the delivery orifice is between 200 and 800 μm, but when the delivery orifice size is increased to 1000μm, the release kinetic is abnormal. Fluid dynamics have an important effect on the delivery rate of propranolol from this device; the delivery rate increases as a function of the fluid flow. The drug release is higher under a turbulent condition with high rate of stirring.     

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.     

Evaluation of two polymeric blends (EVA/PLA and EVA/PEG) as coating film materials for paclitaxel-eluting stent application

The ethylene vinyl acetate copolymer (EVA)/Poly (lactic acid) (PLA) blend and EVA/Poly (ethylene glycol) (PEG) blend were applied as the drug carrier materials for a bi-layer drug-loaded stent coating film, which consisted of a paclitaxel (PTX)-loaded layer and a drug-free EVA layer. The changes of weight and appearance of the drug-free polymeric blend films with increasing time were examined by X-ray diffraction analysis (XRD), gel permeation chromatography (GPC) tests and scanning electronic microscopy (SEM), and the results showed the degradation of PLA and the leaching of PEG from the films. The effects of PLA, PEG and drug contents on in vitro drug release were investigated, and the results demonstrated that the addition of PLA promoted the drug release while the addition of PEG almost did not. Franz cells diffusion test results indicated that the bi-layer structure successfully endowed the stent coating with the release of drug in a unidirectional fashion. The release profiles of films incorporated PTX and the mechanical performance of the film could be customized by readily adjusting the contents of the blend components. Therefore, the polymeric blends could be useful drug carrier materials for drug-loaded stent coating capable of releasing drug in a highly tunable manner.     

Salbutamol Delivering Transdermal Dosage Form Based on Osmo-Regulatory Principle

A transdermal drug delivery system of Salbutamol was developed which released the drug following zero order kinetics. The designed system essentially based on trilaminated matrix concept. The delivery of drug from the system affected by osmotic phenomenon where sodium chloride was used as an osmogent. To establish the desired release rate polyethylene glycol 4000 (PEG 4000) was used as channelising agent in rate controlling membrance of cellulose acetate. The designed systems exhibiting zero-order release rate, were studied for the in-vitro skin permeation. The product which was having skin permeability rate 115 mcg/hr/cm² was selected for the in-vivo evaluation. The forced expiratory volume (FEV₁) and drug plasma concentration were monitored periodically. The study revealed that designed osmoregulatory transdermal drug delivery system of Salbutamol could be used successfully with improved therapeutic response and holds promise for the clinical studies.     

Ketotifen controlled release from cellulose acetate propionate and cellulose acetate butyrate membranes

Ketotifen was immobilised in cellulose acetate propionate (CAP) membranes and in cellulose acetate butyrate (CAB) membranes. The characteristics of each system were evaluated under a range of experimental conditions. The topography and uniformity of the membranes was assessed using scanning electron microscopy. The release characteristics associated with Ketotifen were monitored spectrophotometrically. The swelling capacity of the membranes was evaluated and attributed to the combined effects of diffusion and of complex dissociation, during swelling. The materials produced were able to provide controlled release of Ketotifen due to their controlled swelling behaviour and adequate release properties. The results showed that the release of Ketotifen from the CAB membranes is higher but the release from the CAP membranes is more uniform.     

Preparation,characterization and release of amoxicillin from cellulose acetate and poly(vinyl pyrrolidone) coaxial electrospun fibrous membranes

Electrospinning is a method that has been used to prepare polymeric fibers, with diameters ranging from nanometers to a micrometer of polymers such as cellulose acetate (CA) and poly(vinyl pyrrolidone) (PVP), and to develop membranes with applications in microencapsulation, for controlled release of drugs and for chemical and biological sensors. This work shows the feasibility and optimal conditions for the preparation of fibrous composite membranes of cellulose acetate and poly(vinyl pyrrolidone), via electrospinning, and their morphology; FTIR, and mechanical characterization and the effect of pH on the release of amoxicillin were analyzed. Tubes of CA with diameters around 500 nm were obtained. It was found that the release behavior of the drug from these fibrous membranes was dependent on the pH of the medium. It was observed that the amount of amoxicillin released as a function of time for a pH equal to 7.2 was approximately three times higher than that observed for a pH equal to 3.0. This suggests a greater interaction of amoxicillin with components of the membrane at a pH equal to 3.0, most likely due to the formation of hydrogen bonds. These materials have potential application in gastrointestinal administration and for transdermal patches.     

Cyclodextrin complex osmotic tablet for glipizide delivery

Poorly soluble glipizide was selected as the model drug to prepare osmotic pump tablets (OPT) with proper accessorial material after it was made an inclusion complex by kneading method in order to increase solubility. Polyethylene glycol 4000 (PEG4000) and cellulose acetate (CA) were selected as the coating materials, and acetone-water (95:5) co-solvent was employed as the coating medium. The effects of the osmotic promoting agent, diameter of the drug-releasing orifice, coating composition, and coat weight on the drug release profile were investigated. The drug release profile of the optimal formulation was compared with a commercialized push-pull osmotic tablet. The results indicated that glipizide-cyclodextrin inclusion complex OPT had excellent zero-order release characteristics in vitro.     

纳米纤维素晶/醋酸纤维素共混超滤膜材料的研究

采用浸没沉淀相转化法制备了纳米纤维素晶(CNC)/醋酸纤维素(CA)完全环境友好的共混膜材料,考察了在铸膜液中添加不同质量分数的CNC对共混膜各方面性能的影响。通过超滤装置测定了共混膜的水通量、截留率、含水率和孔隙率;通过万能试验机、环境扫描电子显微镜(SEM)、热重分析仪(TGA)对超滤膜进行了力学性能、形貌结构和热稳定分析。结果表明,随着CNC含量增加,共混膜的孔隙率呈增长趋势,由40.8%提高到66.4%,大孔由原来的规则圆形漏斗状变为狭长椭圆状且互相连通,水通量和拉伸强度呈先上升后减小的趋势。当CNC添加量为0.5%时,共混膜综合性能最优,相比纯CA膜,水通量提高64.7%,拉伸强度提高70%,热稳定性也得到增强。     

Hot melt granulation: a facile approach for monolithic osmotic release tablets

The aim of this work was to develop and evaluate an extended release matrix tablet of glipizide (GP), an oral hypoglycemic agent. Matrices of GP were prepared using microcrystalline cellulose Avicel(?) PH 112, sodium chloride (SC) and polyethylene glycol 6000 (PEG). The content of Kollidon SR (KR), hydroxypropyl methylcellulose K4M premium CR grade (HM) and polyethylene oxide WSR 303 (PO) and/or magnesium hydroxide (MH) was varied in different formulations. All the formulations were processed by hot melt granulation technique. GP release was observed to be influenced by the amount of SC and MH present in the core formulation. The matrix tablets were coated with a solution containing combination of cellulose acetate 398.10 (CA) and PEG. The release of GP was observed to be inversely proportional to the weight of the coating membrane. Matrices containing PO in combination with SC and MH (14.28:8.56) showed significantly higher degree of hydration and swelling that was evident in the surface texture as visualized by scanning electron microscopy (SEM). Results of SEM studies confirmed the presence of pores in the semi-permeable coating membrane from where the GP release would have occurred. The release of GP from this formulation was similar to that of the marketed extended release tablet as judged from similarity factor (f2) analysis, which yielded a value of 74.7. The optimized formulation was found to be stable when tested according to long term and accelerated storage conditions of ICH guidelines upto 3 months.     

Transdermal delivery controlled by a chitosan membrane

The release of a drug from a transdermal delivery system with a rate controlling chitosan membrane was analyzed in vitro and in vivo. Lidocaine hydrochloride, a local anesthetic, was used as the model drug. The in vitro permeability of various chitosan membranes for the drug was investigated using a Franz diffusion cell. Drug release was slower through chitosan membranes with a higher degree of deacetylation (% DD) and with a larger thickness. A transdermal chitosan patch was developed using a chitosan membrane for rate control and a chitosan hydrogel as a drug reservoir. The most prolonged release in vitro was obtained with a 95% DD chitosan rate controlling membrane. The transport mechanism was found to be non-Fickian. The functionality of this transdermal patch was studied on the forearm of human volunteers by assessing the anesthetic effect. Patches with 70% and 95% DD membranes delayed the anesthetic effect, increasing the delay with increasing % DD. It was concluded that a combination of chitosan membrane and chitosan hydrogel is a good transparent system for controlled drug delivery and that the release kinetics in vitro at least for lidocaine have a predictive value for its anesthetic effect in vivo. The demonstration of a direct relationship between in vitro drug membrane permeability and its physiological effect might be considered as quite unique.     

Cellulose acetate microspheres as floating depot systems to increase gastric retention of antidiabetic drug: formulation, characterization and in vitro-in vivo evaluation

Gastric emptying is a complex process that is highly variable and makes the in vivo performance of drug delivery systems uncertain. In order to avoid this variability, efforts have been made to increase the retention time of the drug delivery systems for more than 12 hours utilizing floating or hydrodynamically controlled drug delivery systems. The objective of this investigation was to develop a floating, depot-forming drug delivery system for an antidiabetic drug based on microparticulate technology to maintain constant plasma drug concentrations over a prolonged period of time for effective control of blood sugar levels. Formulations were optimized using cellulose acetate as the polymer and evaluated in vitro for physicochemical characteristics and drug release in phosphate buffered saline (pH 7.4), and evaluated in vivo in healthy male albino mice. The shape and the surface morphology of the prepared microspheres were characterized by optical microscopy and scanning electron microscopy. In vitro drug release studies were performed and drug release kinetics were calculated using the linear regression method. Effects of stirring rate during preparation and polymer concentration on the size of microspheres and drug release were observed. The prepared microspheres exhibited prolonged drug release (more than 10 hours) and remained buoyant for over 10 hours. Spherical and smooth-surfaced microspheres with encapsulation efficiency ranging from 73% to 98% were obtained. The release rate decreased and the mean particle size increased at higher polymer concentrations. Stirring speed affected the morphology of the microspheres. This investigation revealed that upon administration, the biocompatible depot-forming polymeric microspheres controlled the drug release and plasma sugar levels more efficiently than plain orally given drug. These formulations, with their reduced frequency of administration and better control over drug disposition, may provide an economic benefit to the user compared with products currently available for diabetes control.     

Emulsion/Solvent Evaporation as an Alternative Technique in Pellet Preparation

Paracetamol/Eudragit RS, paracetamol/ethylcellulose, and paracetamol/cellulose acetate pellets of different drug/polymer ratios (w/w) were prepared by the dissolution/solvent evaporation technique. These pellets were then characterized by particle size distribution analysis, ultraviolet (UV) spectroscopy, differential thermal analysis, and scanning electron microscopy (SEM). Hard gelatin capsules were filled with each particle size fraction of these pellets, and in vitro dissolution studies were performed to verify the capability of each series of pellets to control drug release. Pellets were spherical, presented a polynucleated microcapsule structure, and under certain experimental conditions, the yield of the preparation process reached very high values. The dissolution studies pointed out the slow paracetamol release from these pellets.     

Controlled-Release Matrix Tablets of Ketoprofen

Abstract

To obtain a prolonged-action dosage form of ketoprofen, 3 different techniques for delaying drug release from hydrophylic matrices of hydroxypropylmethylcellulose were evaluated. They were: the incorporation of glyceryl monostearate, as a release retardant; the partial coating with an impermeable covering of cellulose acetate phthalate; the pan-spray coating with a mixture of insoluble (Eudragit) and soluble (PEG 400) polymers. The in vitro release profiles of each formulation were studied using the USP basket method. Pan-spray coating with the Eudragit-PEG mixture was found to be the best technique, enabling the desired release profile to be obtained through variation of the coating thickness     

Emulsion/solvent evaporation as an alternative technique in pellet preparation

Paracetamol/Eudragit RS, paracetamol/ethylcellulose, and paracetamol/cellulose acetate pellets of different drug/polymer ratios (w/w) were prepared by the dissolution/solvent evaporation technique. These pellets were then characterized by particle size distribution analysis, ultraviolet (UV) spectroscopy, differential thermal analysis, and scanning electron microscopy (SEM). Hard gelatin capsules were filled with each particle size fraction of these pellets, and in vitro dissolution studies were performed to verify the capability of each series of pellets to control drug release. Pellets were spherical, presented a polynucleated microcapsule structure, and under certain experimental conditions, the yield of the preparation process reached very high values. The dissolution studies pointed out the slow paracetamol release from these pellets.     

Cyclodextrin Complex Osmotic Tablet for Glipizide Delivery

ABSTRACT

Poorly soluble glipizide was selected as the model drug to prepare osmotic pump tablets (OPT) with proper accessorial material after it was made an inclusion complex by kneading method in order to increase solubility. Polyethylene glycol 4000 (PEG4000) and cellulose acetate (CA) were selected as the coating materials, and acetone–water (95:5) co-solvent was employed as the coating medium. The effects of the osmotic promoting agent, diameter of the drug-releasing orifice, coating composition, and coat weight on the drug release profile were investigated. The drug release profile of the optimal formulation was compared with a commercialized push–pull osmotic tablet. The results indicated that glipizide–cyclodextrin inclusion complex OPT had excellent zero-order release characteristics in vitro.     

Electrospun sandwich configuration nanofibers as transparent membranes for skin care drug delivery systems

The development of biocompatible nanocomposites for biomedical applications such as drug release has attracted increasing attention in recent years. In this work, electrospun membranes composed of polycaprolactone (PCL) and shellac were fabricated because PCL has favorable mechanical and biological properties, such as high biocompatibility and biodegradability. Meanwhile, shellac is biocompatible and non-toxic; as a result, the fabricated membranes are attractive for controlled drug delivery. Here, PCL/shellac/PCL nanofiber membranes were treated by ethanol vapor to improve their properties for use in drug delivery applications. Salicylic acid was loaded in the drug delivery system as a model drug, and three PCL/shellac/PCL membrane configurations were investigated. Ethanol vapor treatment increased the tensile strength, flexibility, and transparency of the membranes. Both the tensile strength and drug release properties of the membranes strongly depended on the ratio of PCL to shellac.     

Valuation of a Cellulose Acetate (CA) latex as coating material for controlled release products

Cellulose acetate (CA) latex plasticized with 150% triacetin (TA) and 120% triethylcitrate (TEC), based on polymer weight, provided dense and homogeneous films when deposited onto propranolol HCl tablets using conventional fluid bed technology. Film permeability to the drug was low and flux/permeability enhancers were added to the CA structure during its manufacture. Films containing 40% surcrose and 10% PEG 8000 were found to provide the best release characteristics in terms of small lagtime (1 hour) and drug release profile (over 12 hours). When sucrose was added to TA or TEC plasticized fimls, a macroporous membrane was created during exposure to the dissolution fluid due to sucrose release from the film. These observations are consistent with the controlled porosity walls previously described for CA films deposited from organic solvents. It was postulated that drug mass transport occurs mainly within the porous CA structure and the mechanism responsible for its is a combination of molecular diffusion/osmotic pressure via water transport into the porous cellulose acetate membrane. Plasticizer loss during drying had also been demonstrated and related to the change in release profile seen with drying time.     

Controlled drug delivery systems based on thiolated chitosan microspheres

The aim of the present study was to verify the potential of chitosan-thio-butyl-amidine (TBA) microspheres as carrier systems for controlled drug delivery. In this study microspheres were prepared utilizing water in oil (w/o) emulsification solvent evaporation technique. A concentration of 0.5% of chitosan-TBA conjugate displaying 100 µM thiol groups per gram polymer was used in the aqueous phase of the emulsion in order to prepare microspheres. The obtained non-aggregated free-flowing microspheres were examined with conventional light microscope as well as scanning electron microscopy (SEM). The microscopic images indicated that the prepared chitosan-TBA microspheres were of spherical shape and smooth surface while microparticles obtained from the unmodified chitosan were of porous structure and non-spherical shape. Particle size distribution was determined to be in the range from 1 to 59 µm. The free thiol group content of chitosan-TBA microspheres prepared with an aqueous phase of pH 2, 5, and 6.5 were determined to be 71.4, 49.4, and 8.2 µM/g polymer, respectively. Furthermore, results attained from in vitro release studies with fluorescein isothiocyanate labelled dextran (FITC-dextran) loaded chitosan-TBA microspheres showed a controlled release rate for more than three hours while the control reached the maximum peak level of release already within an hour. According to these results, chitosan-TBA microspheres seem to be a promising tool in transmucosal drug delivery for poorly absorbed therapeutic agents.