Entrapment of Phenytoin into Microspheres of Oleaginous Materials: Process Development and in Vitro Evaluation of Drug Release

Abstract

A novel multiparticulate preparation of the antiepileptic agent phenytoin (1) was developed and evaluated in vitro. The preparation consists of gastroresistant microparticulate drug delivery system formulated with oleaginous material (lipospheres) to minimize unwanted effects of l on gastric apparatus. The drug was dispersed in a spherical micromatrix consisting of a mixture of stearyl alcohol and glycerol esters of various fatty acids. The best mixture to obtain discrete, reproducible, free-flowing lipospheres consisted of glyceryl monostearate dilaurate and stearyl alcohol (ratio 3: 17). The lipospheres were obtained by a technique involving melting and dispersion of drug-containing oleaginous material in aqueous medium. The oily droplets of the resulting emulsion after cooling under rapid stirring were transformed into solid. About 99% of the lipospheres were of particle size range 100–800 pm. The lipospheres were analyzed to determine the drug content in various particle sizes and to characterize the in vitro release profile. The average drug content was 23.8% w/w. Drug encapsulation efficiency was about 93.6% and the yield of production ranged from 94 to 98%. The drug discharge pattern from the microparticulate system in the intestinal environment was evaluated. Kinetic results were analyzed to distinguish between various release models. The matrix diffusion-controlled equation was the most appropriate one in describing drug release.     

Preparation and in vitro evaluation of chitosan microspheres containing prednisolone: comparison of simple and conjugate microspheres

The purpose of the present study was to obtain a novel microparticulate formulation of prednisolone, which was adequate for the treatment of inflammatory bowel disease (IBD). The formulations prepared were evaluated in vitro. Two types of chitosan microspheres containing prednisolone, named Ch-Pred and Ch-SP-MS, were prepared by an emulsification-solvent evaporation method using a chitosan-prednisolone mixture and a chitosan-succinyl-prednisolone conjugate (Ch-SP), respectively. Ch-Pred and Ch-SP-MS were obtained in almost spherical shape. Ch-Pred showed a relatively high drug content of 13.2% (w/w), but the particle size was distributed from 10 to 45 µm, and a large initial burst release of approximately 60% was observed. On the other hand, although Ch-SP-MS exhibited a fairly low drug content of 3.5% (w/w), their particle size ranged from several hundred nanometers to 20 µm, with the mean diameter of 5 µm, and a gradual drug release profile was achieved. These characteristics on particle size and in vitro release suggested that Ch-SP-MS should have good potential as a microparticulate system for the treatment of IBD.     

Preparation and In Vitro Evaluation of Chitosan Microspheres Containing Prednisolone: Comparison of Simple and Conjugate Microspheres

The purpose of the present study was to obtain a novel microparticulate formulation of prednisolone, which was adequate for the treatment of inflammatory bowel disease (IBD). The formulations prepared were evaluated in vitro. Two types of chitosan microspheres containing prednisolone, named Ch-Pred and Ch-SP-MS, were prepared by an emulsification-solvent evaporation method using a chitosan-prednisolone mixture and a chitosan-succinyl-prednisolone conjugate (Ch-SP), respectively. Ch-Pred and Ch-SP-MS were obtained in almost spherical shape. Ch-Pred showed a relatively high drug content of 13.2% (w/w), but the particle size was distributed from 10 to 45 µm, and a large initial burst release of approximately 60% was observed. On the other hand, although Ch-SP-MS exhibited a fairly low drug content of 3.5% (w/w), their particle size ranged from several hundred nanometers to 20 µm, with the mean diameter of 5 µm, and a gradual drug release profile was achieved. These characteristics on particle size and in vitro release suggested that Ch-SP-MS should have good potential as a microparticulate system for the treatment of IBD.     

Carnauba Wax Microspheres Loaded with Valproic Acid: Preparation and Evaluation of Drug Release

Abstract

To minimize unwanted toxic effects of valproic acid (1) by the kinetic control of drug release, gastroresistant carnauba wax microspheres loaded with the antiepileptic agent were prepared. The preparation was based on a technique involving melting and dispersion of drug-containing wax in an aqueous medium. The resulting emulsion after cooling under rapid stirring produced solid, discrete, reproducible free flowing microspheres which converted the liquid drug droplets into solid material. About 94% of the isolated microspheres were of particle size range 200-425 μm. The microspheres were analyzed to determine the drug content in various particle size range and to characterize the in vitro release profile. The average drug content was 26% w/w. The intestinal drug discharge of 1 from the carnauba wax microspheres was studied and compared with the release patterns observed for white beeswax and hexadecanol microspheres previously described. The drug release performance was greatly affected by the material used in the microencapsulation process. In the intestinal environment carnauba wax microspheres exhibited more rapid initial rate of release and about 80% of the entrapped drug was discharged in 120 min while complete release occurred in about 8 h.     

Carnauba Wax Microspheres Loaded with Valproic Acid: Preparation and Evaluation of Drug Release

To minimize unwanted toxic effects of valproic acid (1) by the kinetic control of drug release, gastroresistant carnauba wax microspheres loaded with the antiepileptic agent were prepared. The preparation was based on a technique involving melting and dispersion of drug-containing wax in an aqueous medium. The resulting emulsion after cooling under rapid stirring produced solid, discrete, reproducible free flowing microspheres which converted the liquid drug droplets into solid material. About 94% of the isolated microspheres were of particle size range 200-425 μm. The microspheres were analyzed to determine the drug content in various particle size range and to characterize the in vitro release profile. The average drug content was 26% w/w. The intestinal drug discharge of 1 from the carnauba wax microspheres was studied and compared with the release patterns observed for white beeswax and hexadecanol microspheres previously described. The drug release performance was greatly affected by the material used in the microencapsulation process. In the intestinal environment carnauba wax microspheres exhibited more rapid initial rate of release and about 80% of the entrapped drug was discharged in 120 min while complete release occurred in about 8 h.     

Lysozyme-loaded lipid-polymer hybrid nanoparticles: preparation,characterization and colloidal stability evaluation

Context: Lipid-polymer hybrid nanoparticles (LPNPs) are polymeric nanoparticles enveloped by lipid layers, which have emerged as a potent therapeutic nanocarrier alternative to liposomes and polymeric nanoparticles.

Objective: The aim of this work was to develop, characterize and evaluate LPNPs to deliver a model protein, lysozyme.

Materials and methods: Lysozyme-loaded LPNPs were prepared by using the modified w/o/w double-emulsion-solvent-evaporation method. Poly-?-caprolactone (PCL) was used as polymeric core material and tripalmitin:lechitin mixture was used to form a lipid shell around the LPNPs. LPNPs were evaluated for particle size distribution, zeta potential, morphology, encapsulation efficiency, in vitro drug release, stability and cytotoxicity.

Results: The DLS measurement results showed that the particle size of LPNPs ranged from 58.04?±?1.95?nm to 2009.00?±?0.52?nm. The AFM and TEM images of LPNPs demonstrate that LPNPs are spherical in shape. The protein-loading capacity of LPNPs ranged from 5.81% to 60.32%, depending on the formulation parameters. LPNPs displayed a biphasic drug release pattern with a burst release within 1?h, followed by sustained release afterward. Colloidal stability results of LPNPs in different media showed that particle size and zeta potential values of particles did not change significantly in all media except of FBS 100% for 120?h. Finally, the results of a cellular uptake study showed that LPNPs were significantly taken up by 83.3% in L929 cells.

Conclusion: We concluded that the LPNPs prepared with PCL as polymeric core material and tripalmitin:lechitin mixture as lipid shell should be a promising choice for protein delivery.     

Preparation of codeine-resinate and chlorpheniramine-resinate sustained-release suspension and its pharmacokinetic evaluation in beagle dogs

Using ion exchange resins (IERs) as carriers, a dual-drug sustained release suspension containing codeine, and chlorpheniramine had been prepared to elevate drug safety, effectiveness and conformance. The codeine resinate and chlorpheniramine resinate beads were prepared by a batch process and then impregnated with Polyethylene glycol 4000 (PEG 4000), respectively. The PEG impregnated drug resinate beads were coated with ethylcellulose as the coating polymer and di-n-butyl-phthalate as plasticizer in ethanol and methylene chloride mixture by the Wurster process. The coated PEG impregnated drug resinate beads were dispersed in an aqueous suspending vehicle containing 0.5% w/w xanthan gum and 0.5% w/w of hydroxypropylmethylcellulose of nominal viscosity of 4000 cps, obtaining codeine resinate and chlorpheniramine resinate sustained-release suspension (CCSS).

Codeine phosphate and chlorpheniramine maleate were respectively loaded onto AMBERLITE® IRP 69, and PEG 4000 was used to impregnate drug resinate beads to maintain their geometry. Ethylcellulose with di-n-butyl-phthalate in ethanol and methylene chloride mixture for the coating of drug resinate beads was performed in Glatt fluidized bed coater, where the coating solution flow rate was 8-12 g/min, the inlet air temperature was 50-60°C, the outlet air temperature was 32-38°C, the atomizing air pressure was 2.0 bar and the fluidized air pressure was adjusted as required. Few significant agglomeratation of circulating drug resinate beads was observed during the operation. The film weight gained 20% w/w and 15% w/w were suitable for the PEG impregnated codeine resinate and chlorpheniramine resinate beads, respectively. Residual solvent content increased with coating level, but inprocess drying could reduce residual solvent content.

In the present study, the rates of drug release from both drug resinate beads were measured in 0.05M and 0.5M KCl solutions. The increased ionic strength generally accelerated the release rate of both drugs. But the release of codeine from its resinate beads was much more rapid than chloropheneramine released from its resinate beads in the same ionic strength release medium. The drug release specification of the CCSS, where release mediums were 0.05M KCl solution for codeine and 0.5M KCl solution for chlorpheniramine, was established to be in conformance with in vivo performance.

Relative bioavailability and pharmacokinetics evaluation of the CCSS, using commercial immediate-release tablets as the reference preparation, were performed following a randomized two-way crossover design in beagle dogs. The drug concentrations in plasma were measured by a validated LC-MS/MS method to determine the pharmacokinetic parameters of CCSS. This LC-MS/MS method demonstrated high accuracy and precision for bioanalysis, and was proved quick and reliable for the pharmacokinetic studies. The results showed that the CCSS had the longer value of T_max and the lower value of C_max, which meant an obviously sustained release effect, and its relative bioavailability of codeine and chlorpheniramine were (103.6 ± 14.6)% and (98.1 ± 10.3)%, respectively, compared with the reference preparation. These findings indicated that a novel liquid sustained release suspension made by using IERs as carriers and subsequent fluidized bed coating might provide a constant plasma level of the active pharmaceutical ingredient being highly beneficial for various therapeutic reasons.     

Sustained-release pellets of nifedipine using microcrystals combined with MCC-based matrix

The purpose of this study was to prepare sustained-release pellets of nifedipine (NSPs) based on MCC matrix. Wet-milling and extrusion-spheronization techniques were employed to prepare the microcrystals and pellets, respectively. The drug release mechanism and the influencing factors were investigated. After milled with HPMC (E5), the mean particle size of nifedipine in co-grinding mixture (CGM) was 5?μm, which is 15-fold smaller than that of raw material. DSC, X-ray powder diffraction and microscopic observation confirmed the microcrystals of drug were maintained in the CGM. With increased milling time and the content of HPMC, the dissolution rate was greatly enhanced compared with the raw material. The NSPs prepared by MCC and the CGM, which was obtained by cogrinding nifedipine with 5% HPMC solution for 210?min, exhibited sustained release pattern within 8?h. Nifedipine release from MCC-based NSPs followed the Korsmeyer model and closely related to the microstructure of pellet. High stability of NSPs was confirmed after 6 months of accelerated stability test. Using commercially available sustained product as reference, bioequivalence study in beagle dogs was executed and two formulations were bioequivalent. This sustained release pellet formulation of nifedipine was advantageous with convenient and easy scaled-up preparation process.     

Preparation, Characterization and In-Vitro Release Kinetics of Salbutamol Sulphate Loaded Albumin Microspheres

Salbutamol sulphate loaded Bovine serum albumin microspheres were prepared by heat denaturation method. The effects of such preparation conditions as denaturation temperature, denaturation time, protein concentration and phase volume ratio on the extent of drug loading, size and size distribution and drug release were studied. An increase in protein concentration from 5% w/v to 15% w/v increased the mean particle size from 8.5 μm to 16.6 μm and decreased the drug loading from 46% w/w to 18% w/w. A decrease in the phase volume ratio substantially lowered mean particle size and size distribution. An increase in the severity of denaturaion conditions lowered both the drug incorporated and drug released. The kinetics of drug release from microspheres were compared to the theoretical models of Higuchi diffusional release and first order release. Both the models gave an adequate fit to the data. Scanning electron microscopy revealed that the dummy microspheres are spherical with smooth surfaces. As the drug-protein ratio increased, the microspheres exhibited rough surfaces showing the presence of drug crystals.     

Preparation,Characterization and In-Vitro Release Kinetics of Salbutamol Sulphate Loaded Albumin Microspheres

Abstract

Salbutamol sulphate loaded Bovine serum albumin microspheres were prepared by heat denaturation method. The effects of such preparation conditions as denaturation temperature, denaturation time, protein concentration and phase volume ratio on the extent of drug loading, size and size distribution and drug release were studied. An increase in protein concentration from 5% w/v to 15% w/v increased the mean particle size from 8.5 μm to 16.6 μm and decreased the drug loading from 46% w/w to 18% w/w. A decrease in the phase volume ratio substantially lowered mean particle size and size distribution. An increase in the severity of denaturaion conditions lowered both the drug incorporated and drug released. The kinetics of drug release from microspheres were compared to the theoretical models of Higuchi diffusional release and first order release. Both the models gave an adequate fit to the data. Scanning electron microscopy revealed that the dummy microspheres are spherical with smooth surfaces. As the drug-protein ratio increased, the microspheres exhibited rough surfaces showing the presence of drug crystals.     

Preparation of Codeine-Resinate and Chlorpheniramine-Resinate Sustained-Release Suspension and its Pharmacokinetic Evaluation in Beagle Dogs

ABSTRACT

Using ion exchange resins (IERs) as carriers, a dual-drug sustained release suspension containing codeine, and chlorpheniramine had been prepared to elevate drug safety, effectiveness and conformance. The codeine resinate and chlorpheniramine resinate beads were prepared by a batch process and then impregnated with Polyethylene glycol 4000 (PEG 4000), respectively. The PEG impregnated drug resinate beads were coated with ethylcellulose as the coating polymer and di-n-butyl-phthalate as plasticizer in ethanol and methylene chloride mixture by the Wurster process. The coated PEG impregnated drug resinate beads were dispersed in an aqueous suspending vehicle containing 0.5% w/w xanthan gum and 0.5% w/w of hydroxypropylmethylcellulose of nominal viscosity of 4000 cps, obtaining codeine resinate and chlorpheniramine resinate sustained-release suspension (CCSS).

Codeine phosphate and chlorpheniramine maleate were respectively loaded onto AMBERLITE® IRP 69, and PEG 4000 was used to impregnate drug resinate beads to maintain their geometry. Ethylcellulose with di-n-butyl-phthalate in ethanol and methylene chloride mixture for the coating of drug resinate beads was performed in Glatt fluidized bed coater, where the coating solution flow rate was 8–12 g/min, the inlet air temperature was 50–60°C, the outlet air temperature was 32–38°C, the atomizing air pressure was 2.0 bar and the fluidized air pressure was adjusted as required. Few significant agglomeratation of circulating drug resinate beads was observed during the operation. The film weight gained 20% w/w and 15% w/w were suitable for the PEG impregnated codeine resinate and chlorpheniramine resinate beads, respectively. Residual solvent content increased with coating level, but inprocess drying could reduce residual solvent content.

In the present study, the rates of drug release from both drug resinate beads were measured in 0.05M and 0.5M KCl solutions. The increased ionic strength generally accelerated the release rate of both drugs. But the release of codeine from its resinate beads was much more rapid than chloropheneramine released from its resinate beads in the same ionic strength release medium. The drug release specification of the CCSS, where release mediums were 0.05M KCl solution for codeine and 0.5M KCl solution for chlorpheniramine, was established to be in conformance with in vivo performance.

Relative bioavailability and pharmacokinetics evaluation of the CCSS, using commercial immediate-release tablets as the reference preparation, were performed following a randomized two-way crossover design in beagle dogs. The drug concentrations in plasma were measured by a validated LC-MS/MS method to determine the pharmacokinetic parameters of CCSS. This LC-MS/MS method demonstrated high accuracy and precision for bioanalysis, and was proved quick and reliable for the pharmacokinetic studies. The results showed that the CCSS had the longer value of T_max and the lower value of C_max, which meant an obviously sustained release effect, and its relative bioavailability of codeine and chlorpheniramine were (103.6 ± 14.6)% and (98.1 ± 10.3)%, respectively, compared with the reference preparation. These findings indicated that a novel liquid sustained release suspension made by using IERs as carriers and subsequent fluidized bed coating might provide a constant plasma level of the active pharmaceutical ingredient being highly beneficial for various therapeutic reasons.     

Sustained Release Formulation of Salbutamol Sulphate

Sustained release tablets containing salbutamol sulphate has been prepared by wax matrix granulation method and were evaluated for in vitro release profile and in vivo availability studies in dogs. Out of the release retarding waxy materials used combinations of carnauba wax and stearyl alcohol in concentration range between 60 to 70% of the weight of the tablet were found to be optimum in fabricating sustained release tablets for twentyfour hours duration of action. The formulations were also compared with marketed products of salbutamol for in vitro release profile.     

Chitosan-Drug Conjugate Microspheres: Preparation and Drug Release Properties of Microspheres Composed of the Conjugate of 2'- or 3'-(4-Carboxy-butyryl)-5- Fluorouridine with Chitosan

The conjugate microspheres (Chi-glu-FUR-m) were prepared by the dry-in-oil method using chitosan-5-fuorouridine conjugate. Chi-glu-FUR-m were characterized by drug content, particle shape and size, swelling property, and drug release. Their characteristics were compared with those of the simple microspheres (Chi/ FUR-m), which were prepared under similar conditions using a mixture of chitosan and 5-fluorouridine. Both microspheres prepared showed a high retention of the drug after preparation and similar particle size and shape. Swelling ratios after incubation in aqueous buflers of pH 7.4 for 6 hr were similar for both microspheres. Chi-glu-FUR-m swelled quickly in aqueous buffers of pH 7.4 and the disintegration was observed to occur gradually from 24 hr afrer the incubation. Chi-glu-FUR-m showed a gradual drug release (50% release time = 61 hr), while Chi/FUR-m released the drug very rapidly, Such characteristics of Chi-glu-FURm as swelling, slow disintegration, and gradual drug release propose its usefulness for localization or chemoembolization therapy.     

Soluble filler as a dissolution profile modulator for slightly soluble drugs in matrix tablets

The purpose of this experimental work was the development of hydrophilic–lipophilic matrix tablets for controlled release of slightly soluble drug represented here by diclofenac sodium (DS). Drug dissolution profile optimization provided by soluble filler was studied. Matrix tablets were based on cetyl alcohol as the lipophilic carrier, povidone as the gel-forming agent, and common soluble filler, that is lactose or sucrose of different particle size. Physical properties of tablets prepared by melt granulation and drug release in a phosphate buffer of pH 6.8 were evaluated. In vitro studies showed that used filler type, filler to povidone ratio and sucrose particle size influenced the drug release rate. DS dissolution profile could be changed within a wide range from about 50% per 24 hours to almost 100% in 10 hours. The release constant values confirmed that DS was released from matrices by the diffusion and anomalous transport. The influence of sucrose particle size on the drug release rate was observed. As the particle size decreased, the drug release increased significantly and its dissolution profile became more uniform. Soluble fillers participated in the pore-forming process according to their solubility and particle size. Formulations containing 100 mg of the drug, 80 mg of cetyl alcohol, 40 mg of povidone, and 80 mg of either lactose or sucrose (particle size 250–125 μm) were considered optimal for 24-hour lasting dissolution of DS.     

Interfacial Polymerization, A Useful Method for the Preparation of Polymethylcyanoacrylate Nanoparticles

An interfacial polymerization procedure was developed for the preparation of polymethylcyanoacrylate (PMCA) nanoparticles loaded with triamcinolone acetonide. The nanoparticles were characterized concerning their interior structure, size distribution, drug content, drug release and in vivo distribution. These results (except those for the in vivo distribution) were compared with those obtained with nanoparticles prepared by micell polymerization [5]. Both preparation procedures yielded particles with a mean diameter below 500 nm. The drug content of the nanoparticles prepared by interfacial polymerization ranged from 6,5% w/w to 1,9% w/w depending on the employed monomer concentration in contrast to 0,045% w/w for nanoparticles prepared by micell polymerization [5]. In comparison to microcrystalline substance the drug release from the nanoparticles could be sustained in all cases, but there was no difference in drug release between the nanoparticles prepared by both methods.

After removal of surface adherent drug from nanoparticles prepared by both methods those prepared by interfacial polymerization had an about 12 times higher drug content and the remaining drug amount was released more slowly by these particles. Furthermore, using increasing monomer concentrations during interfacial polymerization (125 - 500 mg/100 ml emulsion) drug release was slowed down, but no further improvement could be achieved for monomer concentrations exceeding 250 mg/100 ml emulsion.

After intravenous injection of ^99mTc labeled PMCA nanoparticles into rats they accumulated predominantly in liver, spleen and kidney, a distribution pattern usually found for colloidal particles.     

Evaluation of selected polysaccharide excipients in buccoadhesive tablets for sustained release of nicotine

Some naturally occurring biocompatible materials were evaluated as mucoadhesive controlled release excipients for buccal drug delivery. A range of tablets were prepared containing 0-50% w/w xanthan gum, karaya gum, guar gum, and glycol chitosan and were tested for swelling, drug release, and mucoadhesion. Guar gum was a poor mucoadhesive and lacked sufficient physical integrity for buccal delivery. Karaya gum demonstrated superior adhesion to guar gum and was able to provide zero-order drug release, but concentrations greater than 50% w/w may be required to provide suitable sustained release. Xanthan gum showed strong adhesion to the mucosal membrane and the 50% w/w formulation produced zero-order drug release over 4 hours, about the normal time interval between daily meals. Glycol chitosan produced the strongest adhesion, but concentrations greater than 50% w/w are required to produce a nonerodible matrix that can control drug release for over 4 hours. Swelling properties of the tablets were found to be a valuable indicator of the ability of the material to produce sustained release. Swelling studies also gave an indication of the adhesion values of the gum material where adhesion was solely dependent upon penetration of the polymer chains into the mucus layer.     

Sustained release of piroxicam from solid lipid nanoparticle as an effective anti-inflammatory therapeutics in vivo

Abstract

This study aims to investigate the solid lipid nanoparticle (SLN) as a novel vehicle for the sustained release and transdermal delivery of piroxicam, as well as to determine the anti-inflammation effect of piroxicam-loaded SLN. SLN formulation was optimized and the particle size, polydispersity index, zeta potential (ZP), encapsulation efficiency, drug release, and morphological properties were characterized. The transdermal efficiency and mechanism of the piroxicam-loaded SLNs were investigated in vitro. With the inflammation induced edema model in rat, the anti-inflammatory efficiency of piroxicam-enriched SLNs (Pir-SLNs) was evaluated. The SLN formulation was optimized as: lecithin 100?mg, glycerin monostearate 200?mg, and Tween (1%, w/w). The particle size is around 102?±?5.2?nm with a PDI of 0.262. The ZP is 30.21?±?2.05?mV. The prepared SLNs showed high entrapment efficiency of 87.5% for piroxicam. There is no interaction between piroxicam and the vehicle components. The presence of polymorphic form of lipid with higher drug content in the optimized Pir-SLNs enables the Pir-SLNs to release the drug with a sustained manner. Pir-SLNs with oleic acid as enhancer can radically diffuse into both the stratum corneum and dermal layer, as well as penetrate through the hair follicles and sebaceous glands with significantly higher density than the other control groups. Pir-SLNs promptly inhibited the inflammation since the 3rd hour after the treatment by decreasing the PGE₂ level. SLN was demonstrated to be a promising carrier for encapsulation and sustained release of piroxicam. Pir-SLN is a novel topical preparation with great potential for anti-inflammation application.     

Sustained Release Formulation of Salbutamol Sulphate

Abstract

Sustained release tablets containing salbutamol sulphate has been prepared by wax matrix granulation method and were evaluated for in vitro release profile and in vivo availability studies in dogs. Out of the release retarding waxy materials used combinations of carnauba wax and stearyl alcohol in concentration range between 60 to 70% of the weight of the tablet were found to be optimum in fabricating sustained release tablets for twentyfour hours duration of action. The formulations were also compared with marketed products of salbutamol for in vitro release profile.     

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.     

Production and characterization of hot-melt extruded films containing clotrimazole

Hot-melt extrusion technology (HME) was used to prepare muco-adhesive matrix films containing 10% w/w clotrimazole (CT) intended for local drug delivery applications for the oral cavity. This study was aimed at the production and characterization of these drug delivery systems for the prophylaxis and treatment of oral candidiasis. The film system's formulation contained hydroxypropyl cellulose and poly(ethylene oxide) as polymeric carriers, the bioadhesive polycarbophil, and other excipients. The CT formulation was processed at a temperature range of 125-130 degrees C utilizing a Killion extruder (Model KLB-100) equipped with a 6-inch flex-lip die. The films were evaluated for postextrusion drug content, physical and chemical content uniformity, drug release, thermal and crystalline behavior, and bioadhesive strength. The extruded films demonstrated excellent content uniformity and a postprocessing drug content of 93.3% (+/- 1.0). The degradation product, (o-chlorophenyl)diphenyl methanol, was also identified and quantitated using high performance liquid chromatography. The films were determined to exhibit desirable and consistent release properties and bioadhesive strength (p < 0.05). The results of this study indicate that HME is a viable technique for the preparation of muco-adhesive films containing clotrimazole for oral candidiasis.