Encapsulation Of Water-soluble Drugs Research Articles

Encapsulation of water-soluble drugs in Poly (vinyl alcohol) (PVA)- microparticles via membrane emulsification: Influence of process and formulation parameters on structural and functional properties

Drug-loaded poly (vinyl alcohol) (PVA)-based microparticles have been synthetized by using membrane emulsification and chemical cross-linking. The encapsulation of two water-soluble molecules, catechol (CA) and diclofenac sodium (DS), has been considered as case studies. PVA hydrogels have been recognized as promising biomaterials and suitable candidates for drug delivery. However, the encapsulation of hydrophilic, low molecular weight drugs in particulate materials is currently an ambitious goal. The purpose of this work was to develop high-drug loading systems for hydrophilic molecule delivery based on uniformly distributed particulate carriers. Membrane emulsification has been used as advanced manufacturing method to design drug-loaded PVA microparticles with target properties in terms of particle size, particle size distribution, structure and functional activity. A special emphasis is laid on the important factors that contribute to tune the structured properties of microparticles, encapsulation efficiency/drug loading and drug delivery. In particular, the influence of emulsification method (membrane and homogenizing approaches), phase compositions (PVA concentration, drug concentration, physicochemical properties of drug), cross-linking reaction conditions (cross-linking agent concentration, acidic media) has been studied. Finally, the potential of PVA-based microparticles as drug delivery carriers as well as their in vitro cytotoxicity have been evaluated.

Development and optimization of interpenetrating network beads of delonix regia gum and sodium alginate using response surface methodology

The aim of present investigation was to develop and optimize sustained release interpenetrating network (IPN) beads of delonix regia seed polysaccharide (DRG) and sodium alginate using response surface methodology. Diclofenac sodium (DS) was chosen as model drug. A central composite design was used to study and optimize the effect of independent variables (A: sodium alginate:DRG ratio and B: calcium chloride concentration) on drug encapsulation efficiency (DEE, %) and drug release in 8h (R8h, %). Total thirteen batches of DRG-alginate IPN beads were prepared by ionotropic gelation method using calcium chloride as a cross-linking agent. The DEE (%) of the beads was found in the range 32.79-56.54%. Swelling of beads was high in phosphate buffer (pH 6.8) whereas, less in 0.1 N HCl (pH 1.2). The beads exhibited sustained release of DS for 8h (65.6±0.98 - 99.9±1.87%) and followed Higuchi model demonstrating non-fickian diffusion mechanism. The observed responses of the optimized batch were similar to the predicted values determined by Design Expert (V.7.0, Stat-Ease Inc, USA) software. The optimized DRG-alginate IPN beads may show good encapsulation of water soluble drugs followed by their sustained release for 8h which might be advantageous in terms of advanced patient compliance with reduced dosing interval.

Encapsulation of water-soluble drugs by an o/o/o-solvent extraction microencapsulation method

A new o/o/o-solvent extraction microencapsulation method based on less toxic solvents is presented in this study. The drug is dissolved/dispersed into a poly( d, l-lactide)/or poly ( d, l-lactide-co-glycolide) (PLGA) solution in a water-miscible organic solvent (e.g., dimethylsulfoxide or 2-pyrrolidone) (o 1), followed by emulsification into an oil phase (o 2) (e.g., peanut oil). This emulsion is added to the external phase (o 3) to solidify the drug-containing polymer droplets. The polymer solvent and the oil are extracted in an external phase (o 3) (e.g., ethanol), which is a nonsolvent for the polymer and miscible with both the polymer solvent and the oil. One major advantage of this method is the reduced amount of solvent/nonsolvent volumes. In addition, very high encapsulation efficiencies were achieved at polymer concentration of 20%, w/w for all investigated polymers and o 1/o 2 phase ratios with ethanol as the external (o 3) phase. The encapsulation efficiency was very low (<20%) with water as external phase. The particle size of the microparticles increased with increasing polymer concentration and o 1/o 2 phase ratio and larger microparticles were obtained with 2-pyrrolidone compared to dimethylsulfoxide as polymer solvent (o 1). After an initial burst, in vitro drug release from the microparticles increased for the investigated polymer as follows: Resomer ® RG 506 > RG 756 > R 206. A third more rapid release phase was observed after 6 weeks with Resomer ® RG 506 due to polymer degradation. Similar drug release patterns were obtained with the o/o/o and w/o/w multiple emulsion methods because of similar porous structures. This new method has the advantages of less toxic solvents, much lower preparation volume and solvent consumption and high encapsulation efficiencies when compared to the classical w/o/w method.

Poly(D,L-lactide-co-glycolide) encapsulated poly(vinyl alcohol) hydrogel as a drug delivery system.

The efficiency of encapsulation of water-soluble drugs in biodegradable polymer is often low and occasionally these microcapsules are associated with high burst effect. The primary objective of this study is to develop a novel microencapsulation technique with high efficiency of encapsulation and low burst effect. Pentamidine was used as a model drug in this study. Pentamidine/polyvinyl alcohol (PVA) hydrogel was prepared by freeze-thaw technique. Pentamidine loaded hydrogel was later microencapsulated in poly(lactide-co-glycolide) (PLGA) using solvent evaporation technique. The microcapsules were evaluated for the efficiency of encapsulation, particle size. surface morphology, thermal characteristic, and drug release. Scanning Electron Microscope (SEM) studies revealed that the microcapsules were porous. The microcapsules were uniform in size and shape with the median size of the microcapsules ranging between 27 and 94 microm. The samples containing 10% PLGA showed nearly three times increase in drug loading (18-53%) by increasing the hydrogel content from 0-6%. The overall drug release from the microencapsulated hydrogel, containing 3% and 6% PVA, respectively. was significantly lower than the control batches. The use of a crosslinked hydrogel such as PVA can significantly increase the drug loading of highly water-soluble drugs. In addition. incorporation of the PVA hydrogel significantly reduced the burst effect and overall dissolution of pentamidine.

Evaluation of a Novel Phase Separation Technique for the Encapsulation of Water-Soluble Drugs in Biodegradable Polymer

Biodegradable microcapsules of four water-soluble drugs (pentamidine, captopril, diltiazem, and metoprolol) were prepared using a novel phase separation technique. The microcapsules prepared by this method were irregular in shape. Particle size of the microcapsules was between 60 and 500 pm. The efficiency of encapsulation for all four drugs was more than 40% at 20% drug loading. The encapsulation increased up to 75% or higher when the drug loading was reduced to 5%. The in vitro dissolution was drug dependent. The microcapsules prepared with 5% drug loading showed the minimum dissolution at the end of 24 hr. The initial drug release increased significantly when the drug loading was increased up to 20%. Although the formulations containing 5% drug maintained a sustained-release profile up to 45 days, the formulations containing 10 and 20% drug released more than 50% drug within the first 2 days.

Microencapsulation of Antimicrobial Ceftiofur Drugs

ABSTRACTPolymeric microparticles containing two ceftiofur salts as antimicrobial agents for intramammary application in dry cows were prepared by modified o/w-solvent evaporation methods (dispersion or cosolvent method) or by a w/o/w-multiple emulsion solvent evaporation method. The microspheres were characterized with respect to drug loading, drug release, and morphological properties. The three methods resulted in high encapsulation efficiencies. The choice of organic solvent/solvent mixture strongly affected the structure of the microparticles; both matrix and reservoir-type structures with different porosities were obtained. Scaling up to larger batch sizes resulted in microspheres with a faster drug release. The addition of water-miscible cosolvents to the water-immiscible polymer solution allowed the preparation of microparticles from a drug solution rather than a drug dispersion. Microparticles prepared by the cosolvent method could be separated after shorter time intervals from the aqueous phase; the microspheres had a denser matrix with finely dispersed drug crystals and a slower drug release when compared with microspheres prepared by the dispersion method, which had a more porous structure with larger embedded drug crystals. The cosolvent and dispersion methods present a simple alternative to the w/o/w-solvent evaporation method for the encapsulation of water-soluble drugs with an external water phase.

Encapsulation of water-soluble drugs by a modified solvent evaporation method. I. Effect of process and formulation variables on drug entrapment

Pseudoephedrine HCl, a highly water-soluble drug, was entrapped within poly (methyl methacrylate) microspheres by a water/oil/water emulsification-solvent evaporation method. An aqueous drug solution was emulsified into a solution of the polymer in methylene chloride, followed by emulsification of this primary emulsion into an external aqueous phase to form a water/oil/water emulsion. The middle organic phase separated the internal drug-containing aqueous phase from the continuous phase. Microspheres were formed after solvent evaporation and polymer precipitation. The drug content of the microspheres increased with increasing theoretical drug loading, increasing amounts of organic solvent, polymer and polymeric stabilizer, and decreased with increasing stirring time, increasing pH of the continuous phase and increased volume of the internal and external aqueous phase.

Study of the Growth Control of Nonionic Surfactant Reverse Micelles by Water and Glycerol Using Small-angle X-ray Scattering

This paper described a facile route to the growth control of nonionic surfactant reverse micelles in diglycerol monolaurate (C12G2)/cyclohexane systems at 25°C. Structural characterization of reverse micelles was carried out using small-angle X-ray scattering (SAXS) technique. It has found that C12G2 spontaneously formed elongated prolate type reverse micelles in cyclohexane at 25°C and the micellar size grows with CC12G2 concentration. The reverse micelles could solubilize some amount of water in the micellar core thus enhanced their potential application in the encapsulation of water-soluble drugs. Phase separation occurred with further addition of water. The micelles grow with the amount of water content in the system, as water tends to go to the micellar core swelling the micelles. However, the size decreased with increasing temperature at fixed water content. Increasing mixing fraction of glycerol in water decreased the micellar size. This would be understood as glycerol dehydrates surfactant's headgroup and increased the packing parameter. Keywords: Diglycerol monolaurat;, Cyclohexane; glycerol;, Small-angle X-ray scattering (SAXS), Reverse micelles.DOI: 10.3126/jncs.v24i0.2381Journal of Nepal Chemical Society, Vol. 24, 2009 Page: 12-18