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Biomedical subjects

G Owusu-Ababio

Publications and source records attributed to G Owusu-Ababio.

13 recordsLinked to original sources

Protein release profiles and morphology of biodegradable microcapsules containing an oily core.

The protein release profiles and the morphology of poly(D,L-lactide-co-glycolide) (PLG) and poly(epsilon-caprolactone) (PCL) microcapsules were investigated. The microcapsules were prepared by the (oil(1)-in-oil2)-in-water emulsion solvent evaporation method using bovine serum albumin (BSA) as a model protein. The internal and external morphologies of the microcapsules were examined using a light microscope, scanning electron microscope and a laser scanning confocal microscope. A Coulter counter was used to determine particle size and particle size distribution. Protein quantitation and molecular integrity were performed by the bicinchoninic acid protein assay micro-method and SDS-PAGE, respectively. Microcapsules with a polymeric wall surrounding an oily core containing the protein were formed. The encapsulation efficiency (39-96%) for PLG and (13-90%) for PCL increased with polymer molecular weight and particle volume mean diameter (Vmd). Vmd ranged from 87-128 to 42-157 microm for PLG and PCL, respectively. The protein release profile for PLG microcapsules was either continuous or irregularly pulsatile depending on particle morphology and was completed after cavity breakdown. However, that of PCL microcapsules was essentially irregularly pulsatile and was completed after a longer period of time without cavity breakdown but with significant swelling. There was no detectable cleavage of the protein during 6 months storage of PLG and PCL microcapsules at 4 degrees C. Furthermore, insignificant degradation of protein occurred during in vitro release from PCL microcapsules. In contrast, significant degradation occurred in PLG microcapsules. This approach to microencapsulation of a protein may be promising for the controlled delivery of protein vaccines, and the oil core may enhance the immunogenicity of some weak subunit vaccine candidates.

Capsules↗

Preformulation studies and characterization of the physicochemical properties of amorphous polymers using artificial neural networks.

The utility of artificial neural networks (ANNs) as a preformulation tool to determine the physicochemical properties of amorphous polymers such as the hydration characteristics, glass transition temperatures and rheological properties was investigated. The neural network simulator, CAD/Chem, based on the delta back-propagation paradigm was used for this study. The ANNs software was trained with sets of experimental data consisting of different polymer blends with known water-uptake profiles, glass transition temperatures and viscosity values. A set of similar data, not initially exposed to the ANNs was used to validate the ability of the ANNs to recognize patterns. The results of this investigation indicate that the ANNs accurately predicted the water-uptake, glass transition temperatures and viscosities of different amorphous polymers and their physical blends with a low % error (0-8%) of prediction. The ANNs also showed good correlation between the water-uptake and changes in the glass transition temperatures of the polymers. This study demonstrated the potential of the ANNs as a preformulation tool to evaluate the characteristics of amorphous polymers. This is particularly relevant when designing sustained release formulations that require the use of a fast hydrating polymer matrix.

Alginates↗

In vitro and in vivo characterization of biodegradable enoxacin microspheres.

The in vitro release and plasma concentration profiles of sustained release enoxacin microspheres intended for the treatment of bone and systemic infections due to sensitive strains of bacteria were investigated. Microspheres of enoxacin were prepared by using poly(glycolic acid-co-DL-lactic acid) (PLGA) by the emulsion solvent evaporation technique and characterized by in vitro release in an incubator, and in vivo release in the rat subcutaneous model. The microspheres were spherical in nature, and particle size range had a significant influence on the in vitro release. The enoxacin plasma concentration 2 h after the administration of treatments was two-fold higher in animals who received the free drug compared with those who received microspheres of size range 125-250 microm. The plasma of animals who received the free drug was depleted of enoxacin by the end of the first day. However, the plasma concentration of enoxacin in the animals who received microspheres was sustained above 0.5 microg/ml for about 8 days. The results show that biodegradable microspheres of enoxacin can be prepared which release the antibiotic in vivo for days following a subcutaneous administration. This should provide a means for the sustained treatment of infections due to sensitive strains of bacteria.

Animals↗

Biodegradable progesterone microsphere delivery system for osteoporosis therapy.

The purpose of this study was to formulate and characterize a controlled-release biodegradable delivery system of progesterone for the treatment or prevention of osteoporosis. Microspheres of progesterone were formulated using copolymers of poly(glycolic acid-co-dl-lactic acid) (PGLA 50/50 and PGLA 15/85) and poly(L-lactic acid) (L-PLA) of similar molecular weight by the emulsion solvent evaporation technique. The effects of process variables, such as volume fraction, polyvinyl alcohol (PVA) concentration, polymer composition, and stir speed during preparation, on the yield, encapsulation efficiency (EEF), particle size distribution, in vitro release profiles of progesterone, and surface morphology of progesterone microspheres were investigated. Increasing the volume fraction from 9% to 22% increased the EEF without significantly increasing the yield; however, the rate of progesterone release from the microspheres decreased. Increasing the PVA concentration from 1% to 5% had no significant influence on the EEF, but the rate of progesterone release from microspheres increased. Polymer composition had no significant effect on the EEF, but had a significant effect on the particle size distribution, surface morphology, and release rate of progesterone from the microspheres. Stir speed did not have a significant influence on the EEF; however, stir speed influenced particle size distribution and the rate of progesterone release from microspheres of the same sieve-size range. The results suggest that controlled release of progesterone is possible by varying the different process variables, and that PGLA 50/50 provided the slowest release of progesterone. This should provide a means of delivering progesterone for months for the treatment or prevention of osteoporosis in postmenopausal women.

Antimicrobial Cationic Peptides↗

Effectiveness of ciprofloxacin microspheres in eradicating bacterial biofilm.

The treatment of cultures of planktonic cells and aged biofilm cells of P. aeruginosa and S. aureus with ciprofloxacin (CFX) microspheres of poly(l-lactic acid) (PLA) has been investigated using a modified, open in vitro chemostat system. The kinetics of release of CFX as a function of drug loading and the dose of microspheres were correlated with the rate and extent of killing and eradication of the planktonic cells and biofilm cells cultured on pieces of silicone tubing in the chemostat, respectively. At 71% w/w drug loading, a minimum dose of 7 mg of CFX in microspheres was required to sustain CFX concentration for about 10 h above the minimum inhibitory concentration (MIC) in order to completely eradicate the cells of either bacteria. In contrast, peak concentrations obtained from an equivalent dose of free CFX decreased to low values within 30 min and the bacteria cells were not eradicated. Lower microsphere loadings of CFX were ineffective at the same dose. Thus, this study has identified the formulation requirements for PLA microspheres to sustain CFX concentrations above the MIC for several days in order to eradicate bacteria, particularly aged biofilm cells, in the open chemostat in which the drug is being continually diluted, or similarly at a site of administration, for example, in the peritoneal cavity.

Anti-Infective Agents↗

Effect of solvent composition during preparations on the characteristics of enoxacin microparticles.

We have studied the effect of the solvent system during preparation on the morphology, encapsulation efficiency, and release characteristics of enoxacin microparticles intended for localized delivery to the bone for the treatment of bone infections. Microparticles of enoxacin were formulated using poly(glycolic acid-co-DL-lactic acid) (PGLA) of different viscosity grades by the solvent-evaporation technique. Microparticles prepared with pure dichloromethane had smoother surfaces and less tendency to aggregate than microparticles prepared with dichloromethane-acetone solvent mixtures, which had porous surfaces. Approximately 65% of the microparticles prepared with pure dichloromethane were < 125 microm in diameter compared with 16% (approx.) of microparticles prepared with dichloromethane-acetone mixtures. Increasing the proportion of acetone from dichloromethane-acetone, 10:0, to dichloromethane-acetone, 1:1, resulted in an increase in encapsulation efficiency from 25 to 37%, and an increase in the yield of microparticles harvested from 39 to 51%. Although a further increase in the amount of acetone to dichloromethane-acetone, 1:9, had no significant effect on the yield, aggregation, or fraction of microparticles below 125 microm in diameter, the encapsulation efficiency increased to 56%. Approximately 55% of enoxacin was released in 24 h for microparticles prepared with dichloromethane-acetone, 1:9, compared with 100% release in 10h and 2h for microparticles of the same size range prepared with dichloromethane-acetone, 1:1, and dichloromethane-acetone, 10:0, respectively. The results suggest that the composition of the dichloromethane-acetone solvent system significantly influences the encapsulation efficiency and the rate of release of enoxacin from microparticles. This is important for the formulation of sustained-release enoxacin microparticles for the localized treatment of osteomyelitis.

Acetone↗

Dissolution profiles of flurbiprofen in phospholipid solid dispersions.

This study is concerned with the development of a solid dispersion formulation of flurbiprofen (FLP) and phospholipid (PL) with improved dissolution characteristics. The FLP powders were blended with PL to produce FLP-PL physical mixtures or made into solid dispersions with PL by the solvent method. The FLP exhibited significantly improved dissolution rates in PL coprecipitate (coppt) compared to the physical mixtures or FLP alone. The dissolution studies suggested that less than a 20:1 ratio of FLP to PL was required to disperse FLP completely in the carrier. The coppt yielded a ninefold greater initial dissolution rate. Also, the total amount dissolved after 60 min was twofold greater at a 10:1 ratio of FLP to L-(-dimyristoyl phosphatidylglycerol (DMPG). Similar results were observed with a ratio as low as 20:1 (FLP:DMPG). Increasing the DMPG content did not increase the rate to any significant extent. Thus, a small PL:FLP ratio improved the dissolution to a significant level. Thus, an FLP:PL dispersion may have the clinical advantages of quick release and excellent bioavailability.

Anti-Inflammatory Agents, Non-Steroidal↗

Comparative dissolution studies for mefenamic acid-polyethylene glycol solid dispersion systems and tablets.

The purpose of this study was to enhance the dissolution of mefenamic acid (MFA) through the formation of solid dispersion systems, and to compare the dissolution of the unformulated dispersions with those of formulated dispersions in tablets. Solid dispersions of MFA were prepared in polyethylene glycol 3350 (PEG) as a binary system, and PEG and Tween 20 (TW) as a ternary system by the melt method. The dispersions were characterized by dissolution, scanning electron microscopy, and powder x-ray diffraction studies. A decrease in MFA composition in the binary dispersion systems from 50 to 5% w/w resulted in a 50% increase in the dissolution rate during the period of study, and this was threefold higher than that of pure MFA. Incorporation of TW in the preparation of ternary dispersion systems resulted in a further increase in MFA dissolution. A sevenfold increase in MFA dissolution was observed when the ternary system composition was MFA/PEG/TW 4.7:93:2.3 (% w/w). Scanning electron microscopy and x-ray diffraction pictures showed an increase in size and decrease in crystallinity of the dispersions, respectively. Compression of the dispersions into tablets did not have any effect on the dissolution of the drug from the dispersions. Compression of pure MFA and Avicel PH 101, which was used as a diluent and disintegrant, resulted in a threefold increase in dissolution. However, the dissolution of the uncompressed mixture was identical to that of pure MFA. Thus, further processing of the solid dispersions into tablets did not decrease the rate of dissolution of the drug in the dispersions. This may be very important in the formulation of solid dispersions as tablets, which could lead to a reduction in the dose of practically water-insoluble drugs.

Anti-Inflammatory Agents, Non-Steroidal↗

Efficacy of sustained release ciprofloxacin microspheres against device-associated Pseudomonas aeruginosa biofilm infection in a rabbit peritoneal model.

The relative effectiveness of a poly(L-lactic acid) ciprofloxacin hydrochloride (CIP) microsphere formulation (250-425 microns) against peritoneal implanted biofilm of Pseudomonas aeruginosa was investigated in a rabbit model. Correlations between in-vivo CIP pharmacokinetics in peritoneal dialysate and serum after intraperitoneal administration, in-vivo cell counts and rabbit survival rate were obtained. Dialysate and serum concentrations after 12 h (C12h) were greater than those obtained with free drug whereas maximum serum concentrations (Cmax) were lower and the time to reach Cmax(tmax) was longer. A silastic implant device pre-colonised with P. aeruginosa for 2 days was implanted in the rabbit peritoneum, and dialysate with or without drug or microspheres was administered via a catheter. Rabbits receiving no antibiotic and those receiving free drug (10 mg in dialysate) died of peritonitis and septicaemia, whereas all rabbits given CIP microspheres recovered completely from infection. The viable count of P. aeruginosa was markedly reduced or eliminated from the catheter, the device and the peritoneal wall in CIP microsphere-treated rabbits but not in rabbits treated with free drug, as determined from histological and scanning electronmicroscopic evidence. These results demonstrate that sustained release of antibiotics at biofilm eradication concentrations (BEC) is required to treat biofilm infections associated with peritoneal implanted devices.

Absorption↗

Preparation and characterization of ofloxacin microspheres for the eradication of bone associated bacterial biofilm.

Biodegradable polymers for localized delivery of antibiotics have emerged as an important approach to treating orthopaedic infections. In chronic forms of osteomyelitis which are thought to be associated with bacterial biofilm, localized delivery of a suitable antibiotic is desirable. This paper describes the formulation and in vitro evaluation of biodegradable ofloxacin microspheres for the eradication of bone associated bacterial biofilm infections. Ofloxacin microspheres were formulated using poly(glycolic acid-co-DL-lactic acid) (PGLA) by the emulsion solvent evaporation technique. The effects of process parameters such as phase volume, poly(vinyl alcohol) (PVA) concentration, and viscosity grade of the polymer during preparation on encapsulation efficiency (EEF) and in vitro release profiles were investigated. An increase in the phase volume or volume fraction from 21 to 35% at a constant internal phase volume resulted in an increase in EEF from 34 to 74%. Increasing PVA concentration from 0.25 to 2.5% w/v at a constant phase volume or volume fraction did not have an effect on the EEF. Ofloxacin release from the microsopheres was biphasic with an initial burst release followed by a slow release phase. An optimum slowing down of release was observed when the phase volume was 29%. Above and below this phase volume, release of ofloxacin was higher. The higher the viscosity grade of the polymer used for the preparation of microspheres, the higher the PVA concentration needed to prepare microspheres with slower release. The study indicates that various rates of ofloxacin release is possible by varying formulation conditions. This should provide a means for formulating sustained release microspheres of antibiotics for the treatment of biofilm infections associated with the bone.

Anti-Infective Agents↗

Comparison of in vitro and in vivo release characteristics of sustained release ofloxacin microspheres.

The sustained release nature of ofloxacin microspheres--to eradicate bacterial biofilm associated with chronic infections from sensitive strains of bacteria--was determined both in vitro and in vivo. Ofloxacin microspheres were prepared by emulsion solvent evaporation procedure using poly(glycolic acid-co-dl-lactic acid) (PLGA) as the biodegradable polymer. The microspheres were characterized by scanning electron microscopy, in vitro release in an incubator, and in vivo release in the rat subcutaneous model. The microspheres were highly spherical with a very smooth surface. Approximately 45% of the drug was released from microspheres in sizes of 125-250 microns and 250-425 microns in 2 days compared with approximately 22% from microspheres of size range 37-125 microns indicating that surface area of the microspheres did not control the kinetics of in vitro release. However, about 96% of the drug was released from the three different size ranges in 35 days. The in vitro release profile of microspheres of size range 125-250 microns is not significantly different from microspheres in sizes of 250-425 microns. The peak plasma level of ofloxacin in animals that received the drug suspension occurred within 2 hr and was higher than that of the microspheres that occurred by the end of the second day. The plasma of animals that received the free drug was depleted of ofloxacin by the end of the first day, but the drug was sustained above 0.5 microgram/mL in the plasma of animals that received the microspheres for about 3 weeks. The results suggest that biodegradable ofloxacin microspheres can be prepared that release the antibiotic in vivo for about 3 weeks. This should provide a means for continuous treatment of chronic infections in which bacterial biofilm can occur.

Animals↗

Controlled release tacrine delivery system for the treatment of Alzheimer's disease.

Alzheimer's disease is a neurodegenerative condition that affects approximately 5 million people and is the fourth leading cause of death in America. Tacrine is one of the three drugs approved by the FDA for the treatment of Alzheimer's disease. However, the drug has a short biologic half-life of 2-3 hr and gastrointestinal, cholinergic, and hepatic adverse reactions that are associated with high doses of the drug. The aim of our study was to formulate a controlled release delivery system of tacrine that could be used to minimize the side effects associated with the drug. Microparticles of tacrine were formulated using poly(D,L-lactide-co-glycolide) (PLG). PLG and tacrine were dissolved in mixed organic solvents and added to a polyvinyl alcohol solution that was stirred at a constant rate. The organic solvent was evaporated overnight and the formed microparticles were collected by filtration, dried, and sieve-sized. The effects of such formulation variables, as molecular weight of polymer, stir speed during preparation, and drug loading on encapsulation efficiency (EEF), and in vitro release profiles of tacrine were investigated. An increase in the molecular weight of polymer from 8,000 to 59,000 and 155,000 resulted in approximately 10-fold increase in EEF, but the rate of release decreased with increasing molecular weight. Stir speed during preparation had an effect on the EEF but not on the rate of release. Drug loading did not have a significant effect on the EEF but had an effect on the rate of tacrine release. The results suggest that tacrine could be delivered at controlled levels for weeks for the treatment of Alzheimer's disease.

Alzheimer Disease↗

Formulation and release kinetics of cephalexin monohydrate from biodegradable polymeric microspheres.

Sustained release cephalexin microspheres have been formulated with poly(L-lactic acid) for intraperitoneal administration. Microspheres were prepared with spray-dried cephalexin by phase separation in organic solvent containing a fixed concentration of polymer, then sieve-sized. Batch-to-batch reproducibility of microsphere size distribution and encapsulation efficiency ( > 95%) were demonstrated. The quality of the microspheres was dependent on the rate of stirring during preparation and was highest as 400 rpm. Scanning electron micrographs revealed approximately spherical shapes and porous surfaces. The release of cephalexin followed second order dissolution model kinetics for multiparticulate systems. The apparent second order rate constant, k2, was lowest for the highest sieve-size fraction (250-425 microns) and varied with drug loading reaching a minimum at 33% w/w. A lower molecular weight PLA of 50 000 produced a faster release of cephalexin from microspheres. Cephalexin was released from microspheres for at least 4 h compared to only 10 min for complete dissolution of an equivalent weight of cephalexin powder, indicating sustained release which may be appropriate in treating localized infections.

Cephalexin↗