Formulation and pharmacodynamic evaluation of captopril sustained release microparticles

Cellulose propionate (CP) microparticles containing captopril (CAP) were prepared by solvent evaporation technique. The effects of polymer molecular weight, polymer composition and drug:polymer ratios on the particle size, flow properties, morphology, surface properties and release characteristics of the prepared captopril microparticles were examined. The anti-hypertensive effect of the selected CAP formulation in comparison with aqueous drug solution was also evaluated in vivo using hypertensive rats. The formulation containing drug:polymer blend ratio 1:1.5 (1:1 low:high molecular weight CP), namely F7, was chosen as the selected formulation with regard to the encapsulation efficiency (75.1%), flow properties (theta=24 degrees, Carr index=5%, Hausner ratio=1.1, packing rate=0.535) and release characteristics. Initial burst effect was observed in the release profile of all examined formulations. DSC and SEM results indicated that the initial burst effect could be attributed to dissolution of CAP crystals present on the surface or embedded in the superficial layer of the matrix. The release kinetics of CAP from most microparticle formulations followed diffusion mechanism. After oral administration of the selected microparticle formulation (F7) to hypertensive rats, systolic blood pressure decreased gradually over 24 h compared to reference drug solution. These results may suggest the potential application of cellulose propionate microparticles as a suitable sustained release drug delivery system for captopril.     

Influence of the type of vegetable oil on the drug release profile from lipid-core nanocapsules and in vivo genotoxicity study

Abstract

The use of rice bran (RB), soybean (SB) or sunflower seed (SF) oils to prepare lipid-core nanocapsules (LNCs) as controlled drug delivery systems was investigated. LNCs were prepared by interfacial deposition using the preformed polymer method. All formulations showed negative zeta potential and adequate nanotechnological characteristics (particle size 220–230?nm, polydispersity index < 0.20). The environmental safety was evaluated through an in vivo protocol (Allium cepa test) and LNCs containing RB, SB or SF oils did not present genotoxic potential. Clobetasol propionate (CP) was selected as a model drug to evaluate the influence of the type of vegetable oil on the control of the drug release from LNCs. Biphasic drug release profiles were observed for all formulations. After 168?h, the concentration of drug released from the formulation containing SF oil was lower (0.36?mg/mL) than from formulations containing SB (0.40?mg/mL) or RB oil (0.45?mg/mL). Good correlations between the consistency indices for the LNC cores and the burst and sustained drug release rate constants were obtained. Therefore, the type of the vegetal oil was shown as an important factor governing the control of drug release from LNCs.     

Design and Development of a Novel Controlled Release PLGA Alginate-Pectinate Polyspheric Drug Delivery System

A 23 full factorial design was employed to evaluate and optimize the drug entrapment efficiency and in vitro drug release from PLGA microparticles encapsulated in a complex crosslinked alginate-pectinate matrix (polysphere). The independent formulation variables included the volume of internal and external phases, and concentration of PLGA. Surface morphology and internal structure of PLGA microparticles and polyspheres were examined by scanning electron microscopy which revealed spherical PLGA microparticles with highly porous surfaces that accounted for the rapid burst effect of this system. Texture analysis was used to profile the matrix resilience, tolerance, and energy absorbed. In vitro drug release was assessed in buffer media on PLGA microparticles and polyspheres. Polyspheres exhibited ideal zero-order release while PLGA microparticles had a burst effect followed by lag phase. Kinetic modeling of in vitro drug release data indicated that formulations were not highly dependent on polymeric erosion as a mechanism for drug release but rather diffusion. A close correlation existed between the matrix tolerance and energy absorbed. Formulations with decreased tolerance absorbed less energy, thus led to rapid surface erosion, lower matrix integrity and hence a burst effect. The converse was true for an increased matrix tolerance, which led to zero-order release supported by superior matrix integrity and a significantly reduced burst effect. The rat subcutaneous model validated in vitro release data and demonstrated that the polyspheres provided flexible yet superior rate-modulated drug delivery.     

Preparation and characterization of biodegradable urea-loaded microparticles as an approach for transdermal delivery

This work describes the formulation and characterization of urea-loaded microspheres prepared using various polymers such as ethyl cellulose (EC), cellulose acetate phthalate (CAP) and poly (D,L-lactic-co-glycolic acid) (PLGA), along with the utilization of a solvent evaporation technique. The effect of various formulation parameters (i.e. polymer type and concentration, vehicle type, polymer solution/vehicle volume ratio, drug/polymer ratio, homogenizer and stirrer speed, sonication time and speed, type of washing solution, drying and separation method) on the characteristics of microspheres was also evaluated. Results obtained indicated that, in the presence of urea, highest rate of EC microsphere production could be obtained at a drug/polymer ratio of 1:2 and a polymer solution/vehicle volume ratio of 1:50. In some cases, crystallization of urea was observed during the encapsulation process using cellulose derivative polymers. CAP microparticles showed a rough and tortuous surface while EC microparticles had a wider range of particle size. However, with the PLGA polymer, much better desired microparticles with a smaller size range of 1–3?µm were obtained. In general, PLGA microspheres were spherical in shape and possessed smooth surfaces with less pores in comparison with those obtained by the other polymers. The yield of particle production and the extent of urea encapsulation in PLGA particles were measured to be 68.87%?±?5.3 and 40.5%?±?3.4, respectively. The release study from PLGA microspheres revealed that up to 70% of the drug was released within a few days, through a four-stage release pattern.     

Formulation and evaluation of novel controlled release of topical pluronic lecithin organogel of mefenamic acid

In the present study, pluronic lecithin based organogels (PLO gels) were formulated as topical carrier for controlled delivery of mefenamic acid. Ten organogel formulations were prepared by a method employing lecithin as lipophilic phase and pluronic F-127 as hydrophilic phase in varying concentrations to study various parameters using in vitro diffusion study and in vivo studies. All formulations were found to be off-white, homogenous, and reluctant to be washed easily and have pH value within the range of 5.56–5.80 which is nonirritant. Polymer concentration increased in formulations of F1 to F5 (lecithin) and F6 to F10 (pluronic) resulted in decrease of the gelation temperature, increase of viscosity and reduction of spreadability of gels having polymer tendency to form rigid 3D network. Organogels with higher viscosity were found to be more stable and retard the drug release from the gel. The formulations of F2 and F3 were selected for kinetic studies and stability studies, as they found to have all physical parameters within acceptable limits, highest percent drug content and exhibited highest drug release in eight hours. The order of drug release from various formulations was found to be F2?>?F3?>?F10?>?F4?>?F1?>?F9?>?F8?>?F5?>?F7?>?F6. The optimized formulation F2 was found to follow zero order rate kinetics showing controlled release of the drug from the formulations. In vivo anti-inflammatory activity of optimized mefenamic acid organogel (F2) against a standard marketed preparation (Volini gel) was found satisfactory and significant.     

Preparation of sustained release rifampicin microparticles for inhalation

Objectives The aim of this research was to develop a novel carrier‐free dry powder formulation of rifampicin for inhalation with controlled‐release properties. Methods Rifampicin dihydrate (RFDH) microcrystals were prepared by a polymorphic transformation of rifampicin. The prepared RFDH microcrystals were coated with poly (dl ‐lactide‐co‐glycolide) or poly (dl ‐lactide), using a spray‐dryer equipped with two different types of three‐fluid (3F) spray nozzles. The physicochemical and aerodynamic properties of the coated RFDH microcrystals were compared with those of conventional matrix microparticles. Key findings The coated RFDH powder, encapsulating 50% of rifampicin, was successfully prepared by simple in‐situ coating methods using two different types of 3F nozzles and had mass median aerodynamic diameter values of 3.5–4.5 µm . The thin flaky morphology of RFDH powders, providing good aerosolization properties, was maintained after coating. The coated RFDH formulations showed relatively low initial rifampicin release, compared with the uncoated RFDH crystals, followed by slow rifampicin release (about 70%) over 8 h in phosphate‐buffered saline media (pH 7.4). Significant chemical degradations were not observed from the crystalline‐structured RFDH formulations, while the amorphous‐structured matrix formulations showed chemical degradation in six months. Conclusions These polymer coated RFDH formulations may be a valuable alternative in the treatment of tuberculosis since the carrier‐free formulation offers the benefit of delivering a maximum‐potency formulation of the antibiotic directly to the site of infection, and long drug residence times may be achieved by the controlled release of the drug.     

Preparation of sustained release microparticles with improved initial release property

The objective of this study was to investigate the potential of various formulation strategies to achieve sustained release of the peptide, from injectable poly(D,L-lactide-co-glycolide) (PLGA) and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) microparticles. The microparticles were prepared by a solvent evaporation method. Peptide loaded PLGA microparticles exhibited a pronounced initial burst release (22.3% in 1 day) and lag phase in phosphate buffer of pH 7.0. In contrast, blending of 5.0% TPGS (8.6% release in 1 day) or 10.0% TPGS (5.5% release in 1 day) in PLGA microparticles reduced initial burst release and the lag-phase time. Incorporation of TPGS in PLGA microparticles further increased drug release, attributable to improved drug encapsulation, increased particle size, and exempt of pores. PLGA+ 10.0% TPGS composite microparticles exhibited the most desirable drug release among all the formulations tested, and demonstrated triphasic release after minimal initial burst.     

Novel Biomaterial for Transdermal Application: In vitro and In vivo Characterization

The objective of the present study was to evaluate a novel film forming biomaterial for its potential application in the preparation of unilaminate transdermal adhesive matrix systems. The biomaterial, Damar Batu (DB), was tried alone and in combination with Eudragit RL100 as a matrixing agent in the preparation of transdermal patches. Developed transdermal patches of Diltiazem hydrochloride (DH) were evaluated for thickness uniformity, weight uniformity, folding endurance and drug content. USP dissolution apparatus V was used for in vitro drug release studies. Modified Franz diffusion cell used for permeation study using excised human cadaver skin. Total 6 formulations were developed and on the basis of in vitro drug release and in vitro skin permeation profile F5 composed of DB: Eudragit RL100 (60:40) and carrying 20 %w/w DH was selected as an optimized formulation for in vivo study. The in vivo study results showed that F5 achieved the Cmax of about 269.76?±?1.52?ng/mL in 6?h and sustained the release of the drug till 24?h. The skin irritation study results proved that the novel biomaterial is non-sensitizing and non-irritating. Drug-polymer interaction study carried out to check the compatibility of drug and polymer showed the intactness of the drug in the formulation proving the compatibility of the polymer. It can be proposed from the outcome of the present study that by applying suitable adhesive layer and backing membrane, DB: Eudragit RL100 (60:40) transdermal patches can be of potential therapeutic use.     

Eudragit FS based colonic microparticls of metoprolol tartrate

Metoprolol, a cardioselective β-blocker, is well absorbed in colon after oral administration with mean elimination half life of 3 h with bioavailability 50% due to extensive first pass effect, thus it was aimed to develop its modified release dosage form to reduce dosing frequency. Metoprolol tartrate loaded Eudragit FS microparticles were formulated using solvent evaporation technique by varying polymer contents and then compressing into tablets. The dissolution test was performed in simulated gastrointestinal fluid. All tabletted microparticles were tested for stability after storage in accelerated conditions. As a result of various analytical tests like FTIR, XRD and DSC analyses, drug was found stable in the microparticles. Metoprolol tartrate loaded Eudragit FS tabletted microparticles were stable in accelerated storage conditions. The release behavior of pH-dependent formulations was affected by the dissolution medium pH and the concentration of polymer used. There was a decrease in drug release rate with the increase in polymer concentration. In vitro drug release data (except test formulation F3) were best fitted to zero order model, which indicated the controlled release nature of formulation, while the Korsmeyer-Peppas model explored that drug release occurred according to case II relaxation transport mechanism (n > 0.89). Based on the results, it can be concluded that Eudragit FS is a suitable polymer to design pH dependent microparticles using solvent evaporation technique for the release of drug in colon and T2 can be considered as an optimum formulation on the basis of model independent (f2 test) kinetic interpretation of dissolution results (f2 < 50 for T2 versus reference).     

Biodegradable microparticulate system of captopril

Albumin microparticles have found many applications in diagnosis and treatment in recent years and more than 100 diagnostic agents and drugs have been incorporated into albumin microparticles. In the present study, bovine serum albumin (BSA) based microparticles bearing captopril were prepared by an emulsification-heat stabilization technique. Four batches of microparticles with varying ratio of drug and polymer were prepared. The prepared microparticles were studied for drug loading, particle size distribution, in vitro release characteristics, in vivo tissue distribution study and stability studies. The microparticles had mean diameter between 2 and 11 microm of which more than 70% were below 5 microm and incorporation efficiency of 41-63% was obtained. In vitro release profile for formulations containing captopril-loaded albumin microparticles with heat stabilizing technique shows slow controlled release up to 24 h. The in vivo result of drug-loaded microparticles showed preferential drug targeting to liver followed by lungs, kidneys and spleen. Stability studies showed that maximum drug content and closest in vitro release to initial data were found in the formulation stored at 4 degrees C. In the present study, captopril-loaded BSA microparticles were prepared and targeted to various organs to a satisfactory level and were found to be stable at 4 degrees C.     

Analysis of initial burst in PLGA microparticles

BACKGROUND: This review addresses recent advances in the understanding of the mechanisms that underlie burst release and strategies developed to control burst from poly(lactide-co-glycolide) (PLGA) microparticle formulations. While the initial burst release of drug is not always detrimental, excessive drug release in the burst phase may be toxic, and irregularity in the amount of drug released (e.g., from batch to batch) is not acceptable. Many drugs that are good candidates for sustained release treatments are not miscible in PLGA and common microparticle processing solvents, and, as a result, suffer from excessive initial burst release. OBJECTIVE: The aim of this review is to provide an update on research to understand the mechanisms that underlie burst release of drugs from PLGA microparticles, and strategies developed to control burst. METHODS: This review focuses on literature published since 2004. RESULTS: Strategies to control burst release fall into two general categories. First are efforts to improve the miscibility of drug and polymer by altering the composition of the formulation, for example by altering the salt form of the drug. Secondly, processing methods may be altered (increasing the rate of solvent removal, for example) to prevent drug-polymer separation. The goal of most strategies is to reduce or eliminate burst release, so that the encapsulated drug may be maximally retained in the delivery system for long-term delivery.     

Nasal delivery of antisense oligonucleotides: in vitro evaluation of a thiomer/glutathione microparticulate delivery system

Purpose: The aim of this study was to develop a nasal mucoadhesive microparticulate delivery system for phosphorothioate antisense oligonucleotides (PTO-ODNs) utilizing the thiomer technology.

Methods: PTO-ODN microparticles, coated with either the mucoadhesive polymer polycarbophil-cysteine (PCP-Cys) or unmodified PCP and reduced glutathione (GSH) were prepared by the emulsification solvent evaporation technique. Particle size, drug load, decrease in thiol groups on microparticles, swelling properties, release of incorporated PTO-ODN, and mucoadhesive properties were examined. Permeation enhancing effect of the deployed thiomer conjugate was investigated on excised porcine respiratory mucosa of the nasal cavity.

Results: Results demonstrated that microparticles were almost of spherical structure displaying particle diameter up to 30?μm. In addition, a controlled drug release of the incorporated PTO-ODN was achieved from these particles. Mucoadhesion studies revealed that thiolated PCP-Cys microparticles display 3-fold higher mucoadhesive properties than the corresponding unthiolated polycarbophil microparticles. The uptake of PTO-ODN, incubated in thiolated polycarbophil and glutathione microparticles, from the nasal mucosa was 2.2-fold improved.

Conclusions: According to these results, the thiolated polycarbophil/reduced GSH microparticles might be a promising formulation for systemic delivery of PTO-ODNs via the nasal route.     

<Emphasis Type="BoldItalic">In Vitro</Emphasis> and <Emphasis Type="BoldItalic">In Vivo</Emphasis> Drug Release from a Novel <Emphasis Type="BoldItalic">In Situ</Emphasis> Forming Drug Delivery System

Purpose The objective of this work was to investigate the influence of various preparation and formulation parameters on the in vitro and in vivo release of bupivacaine hydrochloride from an injectable in situ forming microparticle system (ISM). Methods The in vitro drug release of ISM was investigated as a function of various formulation and process parameters and was compared to the drug release from in situ forming implants and conventional microparticles. In vivo studies were carried out in male Sprague–Dawley rats. Results Upon contact with an aqueous medium, the internal polymer phase of the ISM system solidified and formed microparticles. The initial drug release from ISM systems was reduced with decreasing polymer phase/external oil phase ratio. An advantage of the ISM system compared to in situ implant systems was the significantly reduced burst effect, resulting in drug release profiles comparable to microparticles prepared by conventional methods. The in vivo drug release studies were in good agreement with the in vitro drug release. With the ISM system, the analgesic effect of the bupivacaine hydrochloride was prolonged when compared to the injection of a drug solution or drug-polymer solution. Conclusions ISM are an attractive alternative for parenteral drug delivery systems.     

Mechanisms of burst release from pH-responsive polymeric microparticles

Objectives Microencapsulation of drugs into preformed polymers is commonly achieved through solvent evaporation techniques or spray drying. We compared these encapsulation methods in terms of controlled drug release properties of prepared microparticles and investigated the underlying mechanisms responsible for the ‘burst release’ effect. Methods Using two different pH‐responsive polymers with a dissolution threshold of pH 6 (Eudragit L100 and AQOAT AS‐MG), hydrocortisone, a model hydrophobic drug, was incorporated into microparticles below and above its solubility within the polymer matrix. Key findings Although, spray drying was an attractive approach due to rapid particle production and relatively low solvent waste, the oil‐in‐oil microencapsulation method was superior in terms of controlled drug release properties from the microparticles. Slow solvent evaporation during the oil‐in‐oil emulsification process allowed adequate time for drug and polymer redistribution in the microparticles and reduced uncontrolled drug burst release. Electron microscopy showed that this slower manufacturing procedure generated nonporous particles whereas thermal analysis and X‐ray diffractometry showed that drug loading above the solubility limit of the drug in the polymer generated excess crystalline drug on the surface of the particles. Raman spectral mapping illustrated that drug was homogeneously distributed as a solid solution in the particles when loaded below saturation in the polymer with consequently minimal burst release. Conclusions Both the manufacturing method (which influenced particle porosity and density) and drug:polymer compatibility and loading (which affected drug form and distribution) were responsible for burst release seen from our particles     

The preparation of sustained release erythropoietin microparticle

Purpose: Protein microencapsulation in biodegradable polymers is a promising route to provide for sustained release. The erythropoietin (EPO) microparticles are using human serum albumin (HSA) and poly-L-lysine (PK) as the protection complex to increased EPO integrity, entrapped efficiency and active EPO release by w/o/w solvent evaporation techniques. The optimum formulation development process was also reported by using FITC-OVA as a model protein.

Methods: The model protein FITC-ovalbumin and EPO are protected by human serum albumin and poly-L-lysine complex and encapsulated in 50:50 poly(DL-lactide-co-glycolide) by a w/o/w solvent evaporation method. Protein active integrity and degradation compound is measured by size-exclusion chromatography. Protein-loaded microparticle physical properties and in vitro active and degradation compounds release profile are characterized.

Results: High active integrity protein loading efficiency and particle yield of EPO or OVA-HSA/PK-loaded PLG microparticles are successfully produced by a w/o/w solvent evaporation method. Varied protection protein complex formulations and encapsulation processes are investigated. The high OVA model protein loading efficiency (80.2%), FITC-OVA content (0.24?µg?mg^?1) and yield (72.4%) are obtained by adding 100?µg?mL^?1 FITC-OVA complex with 10% HSA/0.05% PK (Mw 1.5–3?kD) in the initial solution to protect the model protein. In vitro release profiles show more active OVA release from HSA/PK OVA-loaded than OVA-loaded only microparticles and also the amount of degraded protein that comes out after 3 weeks incubated in the PBS medium for OVA-loaded only microparticles is observed. The same formulation and preparation process resulted in EPO loading efficiency (68.4%), EPO content (0.23?µg?mg^?1) and yield (76.1%) for HSA/PK EPO-loaded microparticles. In vitro release profiles show active EPO sustained release over 7 days. Using HSA/PK as carried in the primary emulsion of EPO-loaded microparticles resulted in less burst release% than EPO-loaded only microparticles.     

The characteristics of betamethasone-loaded chitosan microparticles by spray-drying method

Betamethasone (BTM)-loaded microparticles prepared by a spray drying method using chitosan (CTS) as raw material, type-A gelatin and ethylene oxide-propylene oxide block copolymer (Pluronic F68) as modifiers. The BTM-loaded in varied chitosan/Pluronic F68/gelatin microparticle formulations was investigated. By properly choosing excipient type and concentration a high degree of control was achieved over the physical properties of the BTM-loaded microparticles. Microparticle characteristics (zeta potential, tap density, particle size and yield), loading efficiencies, microparticle morphology and in-vitro release properties were examined. Surface morphological characteristics and surface charges of prepared microparticles were observed by using scanning electron microscopy (SEM) and microelectrophoresis. A SEM micrograph shows that the particle sizes of the varied chitosan composed microparticles ranged from 1.1-4.7 microm and the external surfaces appear smooth. The BTM-loaded microparticles entrapped in the chitosan/Pluronic F68/gelatin microparticles with trapping efficiencies up to 93%, collected yield rate 44%, and mean particle size varied between 1-3 microm, positive surface charge (20-40 mv), and tap densities (0.04-0.40 g/cm3) were obtained. The collected BTM yield and size of particle was increased with increasing BTM-loaded amount but both zeta potential and tap density of the particles decreased with increasing BTM-loaded amount. The in vitro release of BTM showed a dose-dependent burst followed by a slower release phase that was proportional to the drug concentration in the concentration range between 5-30%w/w. The in vitro drug release from the chitosan/Pluronic F68/gelatin 1/0.1/0.4 microspheres had a prolong release pattern. These formulation factors were correlated to particulate characteristics for optimizing BTM microspheres in pulmonary delivery.     

Preparation and characterization of metformin hydrochloride loaded-Eudragit®RSPO and Eudragit®RSPO/PLGA nanoparticles

The aim of the present study was to develop and characterize metformin HCl-loaded nanoparticle formulations. Nanoparticles were prepared by the nanoprecipitation method using both a single polymer (Eudragit^®RSPO) and a polymer mixture (Eudragit/PLGA). The mean particle size ranged from 268.8 to 288?nm and the nanoparticle surface was positively charged (9.72 to 10.1 mV). The highest encapsulation efficiency was observed when Eudragit®RSPO was used. All formulations showed highly reproducible drug release profiles and the in vitro drug release in phosphate buffer (pH?=?6.8) ranged from 92 to 100% in 12?h. These results suggest that Eudragit^®RSPO or Eudragit/PLGA nanoparticles might represent a promising sustained-release oral formulation for metformin HCl, reducing the necessity of repeated administrations of high doses to maintain effective plasma concentrations, and thus, increasing patient compliance and reducing the incidence of side-effects.     

Testosterone solid lipid microparticles for transdermal drug delivery. Formulation and physicochemical characterization

Purpose: The main objective of the study was to formulate and characterize testosterone (TS) solid lipid microparticles (SLM) to be applied as a transdermal delivery system.

Methods: Testosterone SLMs were formulated using an emulsion melt homogenization method. Various types and concentrations of fatty materials, namely glyceryl monostearate (GM), glyceryl distearate (GD), stearic acid (SA) and glyceryl behanate (GB) were used. The formulations contained 2.5 or 5?mg TS?g^?1. Morphology, particle size, entrapment efficiency (EE), rheological properties and thermal behaviour of the prepared SLM were examined. In vitro release characteristics of TS from various prepared SLM were also evaluated over 24?h using a vertical Franz diffusion cell. In addition, the effect of storage and freeze-drying on particle size and release pattern of TS from the selected formulation was evaluated.

Results: The results indicated that the type of lipid affected the morphology and particle size of SLM. A relatively high drug percentage entrapment efficiency ranging from 80.7–95.7% was obtained. Rheological studies showed plastic flow characteristics of the prepared formulations. DSC examination revealed that TS existed in amorphous form in the prepared SLM. Release studies revealed the following rank order of TS permeation through cellophane membrane after application of various formulations: 5% GM?<?5% GD?<?5% SA?<?5% GB?<?2.5% GM?<?2.5% SA?<?10% GD?<?10% GB. The drug permeation through excised abdomen rat skin after application of 10% GB–2.5?mg TS?g^?1 SLM was lower than that permeated through cellophane membrane. Moreover, SLM containing 10% GB–2.5?mg TS?g^?1 stored at 5°C showed good stability as indicated by the release study and particle size analysis. Trehalose showed high potential as a cryoprotectant during freeze drying of the selected SLM formulation.

Conclusions: The developed TS SLM delivery system seemed to be promising as a TS transdermal delivery system.     

Reduction in burst release of PLGA microparticles by incorporation into cubic phase-forming systems

A high initial burst release of an phosphorothioate oligonucleotide drug from poly(lactide-co-glycolide) (PLGA) microparticles prepared by the w/o/w solvent extraction/evaporation was reduced by incorporating the microparticles into the following glycerol monooleate (GMO) formulations: 1) pure molten GMO, 2) preformed cubic phase (GMO + water) or 3) low viscosity in situ cubic phase-forming formulations (GMO + water + cosolvent). The in situ cubic phase-forming formulations had a low viscosity in contrast to the first two formulations resulting in good dispersability of the microparticles and good syringability/injectability. Upon contact with an aqueous phase, a highly viscous cubic phase formed immediately entrapping the microparticles. A low initial burst and a continuous extended release over several weeks was obtained with all investigated formulations. The drug release profile could be well controlled by the cosolvent composition with the in situ systems.     

Design,in vitro and in vivo evaluation of glipizide Eudragit microparticles

Glipizide microparticles made with Eudragit (RS 100 and RL 100), prepared by emulsion solvent evaporation technique were evaluated for various in-vitro properties viz. encapsulation efficiency, particle size and surface morphology, drug release pattern and in-vivo hypoglycaemic activity. The optimized formulation parameters were used to prepare smooth and spherical microparticles (2–32 µm) with higher entrapment efficiency (67–89%). Drug release patterns of glipizide microparticles of Eudragit RS 100 and Eudragit RL 100 with drug-to-polymer ratio of 1 : 4 (i.e. EGM14 and ELGM14) have shown gradual and extended release for 24 h with cumulative release of glipizide to the extent of 72.3% and 83.9%, respectively. However, EGM14 showed a significant in-vivo hypoglycaemic effect up to 12 h in rabbits while ELGM14 showed for 9 h. Hence, glipizide microparticles of Eudragit RS 100 (glipizide: polymer 1 : 4) is better suited for oral sustained release formulation.