Effects of process variables on micromeritic properties and drug release of non-degradable microparticles

Introduction: The purpose of this investigation was to evaluate microencapsulated controlled release preparation of theophylline using Eudragit RS 100 as the retardant material with high entrapment efficiency. Methods: Microspheres were prepared by the emulsion-solvent evaporation method. A mixed solvent system consisting of methanol and acetone and light liquid paraffin as oily phase were chosen. Sucrose stearate was used as the surfactant to stabilize the emulsification process. The prepared microspheres were characterized by drug loading, Fourier-transform infrared spectroscopy (FTIR), differential scanning colorimetry (DSC) and scanning electron microscopy (SEM). The in vitro release studies were performed at pH 1.2 and 7.4 aqueous medium. Results: Increasing the concentration of emulsifier, sucrose fatty acid ester F-70, decreased the particle size which contributed to increased drug release rate. The drug loading microparticle Eudragit RS100(1:6) showed 60-75% of entrapment and mean particle size 205.93-352.76 μm.The results showed that, an increase in the ratio of polymer: drug (F5, 6: 1) resulted in a reduction in the release rate of the drug which may be attributed to the hydrophobic nature of the polymer. Conclusion: The release of theophylline is influenced by the drug to polymer ratio and particle size. Drug release is controlled by diffusion and the best-fit release kinetic is Higuchi model. © 2011 by Tabriz University of Medical Sciences

Novel Pentablock Copolymers as Thermosensitive Self-Assembling Micelles for Ocular Drug Delivery

Many studies have focused on how drugs are formulated in the sol state at room temperature leading to the formation of in situ gel at eye temperature to provide a controlled drug release. Stimuli-responsive block copolymer hydrogels possess several advantages including uncomplicated drug formulation and ease of application, no organic solvent, protective environment for drugs, site-specificity, prolonged and localized drug delivery, lower systemic toxicity, and capability to deliver both hydrophobic and hydrophilic drugs. Self-assembling block copolymers (such as diblock, triblock, and pentablock copolymers) with large solubility variation between hydrophilic and hydrophobic segments are capable of making temperature-dependent micellar assembles, and with further increase in the temperature, of jellifying due to micellar aggregation. In general, molecular weight, hydrophobicity, and block arrangement have a significant effect on polymer crystallinity, micelle size, and in vitro drug release profile. The limitations of creature triblock copolymers as initial burst release can be largely avoided using micelles made of pentablock copolymers. Moreover, formulations based on pentablock copolymers can sustain drug release for a longer time. The present study aims to provide a concise overview of the initial and recent progresses in the design of hydrogel-based ocular drug delivery systems

Natural Polysaccharide based Nanoparticles for Drug/Gene Deliv­ery

The dawn of the state-of-the-art methods of drug/gene delivery, nano-based delivery systems for delivery of pharmaceutically active agents into the target sites in the body have been developed. Among these, a concerted effort has been directed towards the development of biodegradable/biocompatible nanomaterials with the high potential benefits of passive/active targeting and reduced undesirable side effects. Since polysaccharides offer a large number of available reactive groups, specific targeting could be obtained by the surface coating of nanoparticles with targeting ligands. On the other hand, mucoadhesive properties of polysaccharides can be used for prolonging the residence time of delivery systems at the site of absorption. This study reviews a number of important polysaccharides with a perspective on the challenges, advantages, and disadvantages of their applications as drug/gene delivery systems

Development and chemical stability studies of alcohol-free Phenobarbital solution for use in pediatrics

Phenobarbital an anticonvulsant drug and tranquilizer, is frequently used in pediatric medicine usually as an oral solution. Due to the poor aqueous solubility, ethanol has been used as a cosolvent for increasing the solubility of Phenobarbital. Nowadays, there is a tendency to eliminate ethanol from oral preparations in general, particularly in pediatric medicine. Therefore, the aim of the present study was to investigate the solubility of Phenobarbital in various oral cosolvents and to present ethanol-free oral solution of Phenobarbital for pediatrics. The chemical stability of the solutions was also investigated. In this research, mixtures of water, propylene glycol and glycerin were prepared with different ratios to obtain optimum solubility where crystallization and crystal growth did not occur at 4 ?C for a period of 2 months and the pH of the solutions was adjusted at 4.5. The results showed that only formulations containing 10-12% propylene glycol, 26-28% glycerin and 0-20% water had no crystal growth. Chemical stability (shelf-life) of the selected formulations was investigated using Arrhenius accelerated stability test. The chemical stability results showed that these formulations were stable over the period of 2 years

Comparative study of in vitro release and mucoadhesivity of gastric-compacts composed of multiple unit system/bilayered discs using direct compression of metformin hydrochloride

Introduction: Metformin is an oral anti-diabetic drug in the biguanide class. The goal of this study was to develop gastric-retentive MH discs in order to prolong the retention of drug in gastric mucosa.Methods:Two groups of metformin hydrochloride (MH) mucoadhesive gastroretentive discs were prepared: (a) bilayered discs prepared by direct compression of powders containing polymers as Carbopol 934P (CP, mucoadhesive polymer) and ethylcellulose (EC, rotardant polymer), (b) multiple unit system (microparticle) discs prepared by the emulsification, solvent evaporation, and compression technique from microparticles using polymers CP and EC. Gastric-mucoadhesive compacts were evaluated by investigating their release pattern, swelling capacity, mucoadhesion property, surface pH, and in vitro gastro-retentive time. Discs formulation was subjected to disintegration and dissolution tests by placing in 0.1 M hydrochloric acid for 8 h. Results: The production yield showed F2 microparticles of 98.80%, mean particle size of 933.25 µm and loading efficiency of 98.44%. The results showed that prepared microparticle discs had slower release than bilayered discs (p>0.05). The bilayered discs exhibited very good percentage of mucoadhesion. The results also showed a significant higher retention of mucoadhesive bilayered discs in upper gastrointestinal tract (F´1, 1:2 ratio of CP:EC). Histopathological studies revealed no gastric mucosal damage.Conclusion: Mucoadhesive multiple unit system/bilayered discs interact with mucus of gastrointestinal tract and are considered to be localized or trapped at the adhesive site by retaining a dosage form at the site of action as well as improving in the intimacy of contact with underlying absorptive membrane to achieve a better therapeutic performance of anti-diabetic drug

Mucoadhesive and Drug Release Properties of Benzocaine Gel: Properties of benzocaine gel

Gel dosage forms are successfully used as drug delivery systems considering their ability to control drug release and to protect medicaments from a hostile environment. The aim of this work was to investigate the properties of carbopol 934P polymeric system in water-misible cosolvents such as glycerin and alcohol. Benzocaine is a local anesthetic and the mucosal gel formulation is applied in the treatment of dental pain. Samples were prepared by simply dispersing different amounts of Carbopols (0.5-3%) into the alcoholic solution at the room temperature and were kept at 4, 25 and 40 °C. All these systems were then characterized for distribution, bioadhesiveness on the mucosa, physical stability and drug release. The silastic membrane was employed. The membrane must not be a barrier for drug transport. Franz diffusion cell used to study in vitro drug release. The increase in carbopol concentration caused increased viscosity and bioadhesiveness. Neutralization of pH in various concentrations of carbopol gels showed resulted in increased viscosity. A relationship between the viscosity and bioadhesive strength was shown in the neutralized carbopol gels. On the other hand, the results indicated that increasing amount of alcohol and glycerin reduced drug release. In contrast, by increasing the amount of water, elasticity and release rate was increased. Vision-gel® was used as a reference for comparison with the oromucosal gel formulation. The results showed that diffusion of benzocaine from oromucosal gel and commercial sample followed Higuchi law

Control of encapsulation efficiency in polymeric microparticle system of tolmetin

Ethylcellulose microparticles containing tolmetin sodium, an anti-inflammatory drug, were prepared by a solvent diffusion method based on the formation of multiple W/O1/O2-emulsion. The drug used was TOL, which is water-soluble and n-hexane was used as the non-solvent. Important parameters in the evaluation of a microencapsulation technique are actual drug loading, the encapsulation efficiency, the yield, solvent systems, dispersed phase to continuous phase ratio (DP/CP ratio), composition of continuous phase, drug distribution in microparticles and stability of primary emulsion. A small volume of internal aqueous phase and volume of organic solvent were favorable to achieve high drug encapsulation efficiencies. Since drug release during the initial stages depends mostly on the diffusion escape of the drug, major approaches to prevent the initial burst have focused on efficient encapsulation of the drug within the microparticles. For this reason, control of efficiency and the extent of initial burst are based on common formulation parameters. Most parameters affect encapsulation efficiency and initial burst by modifying solidification rate of dispersed phase. In order to prevent many unfavorable events such as pore formation, drug loss, and drug migration that occur while the dispersed phase is in the semi-solid state, it is important to understand and optimize these variables

Preparation and In Vitro/Ex Vivo Evaluation of Buccoadhesive Discs of an Anti-Parkinson Drug: Relationship between Mucoadhesivity, Drug Release and Permeability

Background: Selegiline hydrochloride (Sel) is a drug applied for the therapy of early-step Parkinson's disease. In usual clinical doses, it is an elective irreversible MAO-B inhibitor. This study intended to formulate mucoadhesive microspheres of selegiline with the objective of improving the therapeutic efficacy, patient compliance and bioavailability. Methods: The microspheres were prepared by emulsion solvent evaporation method (O1/ O2) using hydroxypropyl methylcellulose (HPMC). In the current study, bucco-adhesive microspheres were prepared with different drug to polymer ratios and characterized by encapsulation efficiency, particle size, Differential Scanning Calorimetry (DSC), FTIR Fourier Transform Infrared Spectroscopy (FTIR), flowability, the degree of swelling and surface pH, mucoadhesive character, retentive time, and drug release studies. Results: The best drug to polymer ratio in microspheres was 1:2 (as F1). The production yield microspheres F1 showed production yield of 84.79%, mean particle size of 744.73 μm and loading efficiency of 53.33%. The DSC exhibited the property of selegiline loaded microspheres changed to amorphous form. The FTIR spectrum proposed that the drug kept its chemical stability during the emulsification process. The results showed that the microspheres of F1 had faster release than the microspheres of F2 (1:4), F3 (1:6), and commercial tablet (p<0.05). The microspheres did not exhibit good retention time properties (276.66 329.66 min). The results of mucoadhesion strength (8.3 18.3 g/cm2) and surface pH of discs (6.44 6.97) showed the better characterization of microspheres in buccal. Conclusion: The formulations were found to be appropriate candidates for the improvement of microspheres for the remedial objects

Preparation and evaluation of PCL-PEG-PCL micelles as potential nanocarriers for ocular delivery of dexamethasone

Objective(s): Micelles have been studied as nanoparticulate drug delivery systems for improving the topical ocular delivery of hydrophobic drugs. The objective of this study was to develop and characterize dexamethasone-loaded polycaprolactone-polyethylene glycol-polycaprolactone (PCL-PEG-PCL) micelles to improve patient compliance and enhance the ocular bioavailability of poorly water-soluble drugs. Materials and Methods: The PCL-PEG-PCL copolymers were synthesized via the ring opening polymerization of ε-caprolactone in the presence of PEG. The resulting purified copolymers were characterized by GPC, NMR, FTIR, XRD and DSC. The critical micelle concentrations (CMCs) of the copolymers mentioned were determined. Dexamethasone was loaded into polymeric micelles by film hydration method, and dexamethasone-loaded micelles were characterized by TEM and DLS. Drug release kinetics and ex vivo corneal permeability were also determined. Results: The CMC of the synthetized copolymers was approximately 0.03 mg/ml. Aqueous solutions of the resulting copolymers (400 mg/ml) rapidly formed a gel in situ at 34 °C. The TEM results exhibited the successful formation of spherical micelles. The size of the prepared micelles was approximately 40 nm. Formulated micelles sustained the release of the incorporated dexamethasone for 5 days. Conclusion: Data from ex vivo permeability tests indicated that PCL-PEG-PCL micelles can be suitable candidates for the ocular delivery of dexamethasone and, likely, other hydrophobic drugs