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Biomedical subjects

R Jalil

Publications and source records attributed to R Jalil.

14 recordsLinked to original sources
PubMed1990

[Human recombinant erythropoietin (rH-EPO) in chronic hemodialysis patients].

We studied 7 patients on chronic hemodialysis before and after 12 weeks of therapy with human recombinant erythropoietin. The drug was administered intravenously, 3 times a week at doses increasing from 50 to 125 U/kg. Dialysis was performed for 4 hr, 3 times a week and no blood transfusions were used during the study. An increased tolerance to daily physical activities was observed in all patients. Hematocrit increased from 19 +/- 3.4 to 28 +/- 4.1 and hemoglobin from 6.7 +/- 1.3 to 9.4 +/- 1.5, p less than 0.01. No changes were detected in blood pressure, weight, liver function tests and nutritional values. No patient developed either absolute (ferritin less than 30 ng/ml) or relative iron deficiency (transferrin saturation less than 20%) during the study. Efficiency of dialysis remained unaltered. No secondary effects from the drug were observed. Thus, this study confirms the clinical usefulness of human recombinant erythropoietin in patients with chronic renal failure and anemia on chronic dialysis.

Adult↗
PubMed1990

[Myelodysplasias: clinical experience with 35 patients].

Myelodysplasia, characterized by varied reductions of peripheral blood elements with normal or hypercellular bone marrow, is relatively frequent among older patients and may evolve to acute leukemia. We reviewed findings in 35 patients whom, according to the FAB classification were distributed as follows: simple refractory anemia (RA) 34%, sideroblastic refractory anemia (SRA) 14%, refractory anemia with excess blast forms (RAEB) 31%, chromic myelomonocytic leukemia (CMML) 12% and refractory anemia with excess blast forms in transformation (RAEBT) 9%. Cytogenetic studies performed in 16 patients were abnormal in 5 (31%), all among patients with poor prognosis forms of the disorder. All patients had anemia; thrombopenia and neutropenia were more frequent in subtypes RAEB, CMML and RAEBT). Mean survival rate was 30 months, significantly greater in RA and SRA compared to the other groups. Infections and development of acute leukemia were the causes of death.

Actuarial Analysis↗
PubMedDate not supplied

Microencapsulation using poly(L-lactic acid). I: Microcapsule properties affected by the preparative technique.

Microcapsules were prepared using a poly (L-lactic acid) (L = PLA), mol. wt. 43,200, by an emulsification and solvent evaporation technique. Phenobarbitone (PB) was used as a reference drug, (core to polymer ratio, 1:1). Both the o/w and w/o emulsion system were investigated in order to study microcapsule properties affected by the preparative technique. In the o/w system, dichloromethane (DCM) was used to dissolve L = PLA and PB and the resulting solution was dispersed in 1 per cent aqueous gelatin solution. Subsequent evaporation of the DCM resulted in the formation of microcapsules. PB was found to be poorly encapsulated within microcapsules from this o/w system. PB content in the microcapsules was found to improve using PB saturated aqueous gelatin solution as the continuum. In the w/o system, acetonitrile (AN) was used as a solvent for L-PLA and PB and light liquid paraffin (LLP), containing 2 per cent w/w Span 40, as the continuous phase. PB loading in the microcapsules was found to be very high from this w/o system. Microcapsules from the o/w system were very small compared to microcapsules obtained from the w/o system. The morphology of the microcapsules and the surface properties were found to be affected distinctly by the two techniques. Microcapsules from the o/w system showed a smooth and less porous surface, whereas a highly porous surface containing embedded PB crystals was found in the microcapsules from the w/o system.

Capsules↗
PubMedDate not supplied

Microencapsulation using poly(DL-lactic acid). I: Effect of preparative variables on the microcapsule characteristics and release kinetics.

Poly(DL-lactic acid) (DL-PLA, molecular weight 20,500) microcapsules containing phenobarbitone (PB) as a reference core were prepared using a water/oil (W/O) emulsion system. Surface morphology, particle size and 'encapsulation efficiency' of the microcapsules prepared using different preparative variables have been investigated. Buffer pH 9 was used as a dissolution medium to determine the affect of preparative variables on the release rate from these microcapsules. With an increase in temperature of evaporation the microcapsule surface became increasingly irregular and porous, due to deposition of phenobarbitone crystals near the vicinity of the microcapsule surface leading to rapid release of the core. The normalized release rate was found to increase exponentially with an increase in the temperature of evaporation. Microcapsule morphology was also severely affected due to differences in polymer concentration in the disperse phase solvent. With the increase in polymer concentration, the microcapsule surface was found to be increasingly irregular and non-continuous, due to rapid precipitation of the polymer. Increased polymer concentrations also increased mean microcapsule diameter. The release rate increased with the increase in polymer concentration due to surface defects and did not exhibit a straight line correlation. When core loading was very high (e.g. C:P, 2:1 and 1:1), crystals of phenobarbitone appeared at the surface and these caused a very rapid burst effect. However, microcapsules containing a lower phenobarbitone content were found to follow t1/2 dependent release. The encapsulation efficiency was not seriously affected due to variations in temperature of preparation and polymer concentration. However, with the decrease in initial core loading the encapsulation efficiency of microcapsules was found to be reduced.

Chemical Phenomena↗
PubMedDate not supplied

Microencapsulation using poly(DL-lactic acid). II: Effect of polymer molecular weight on the microcapsule properties.

Poly(DL-lactic acid) (DL-DPA) of three different molecular weights, 20,500; 13,300 and 5200, was used to prepare microcapsules containing differing contents of phenobarbitone (PB), as a reference core. A water/oil (W/O) emulsion evaporation method was used. The effect of polymer molecular weight on the particle size, 'encapsulation efficiency', morphology, density, thermal behaviour and swelling property has been reported. A general trend towards lowering the mean microcapsule size, both by volume and population, was observed with respect to lower polymer molecular weight. The gross morphology of the microsapsule surface, encapsulation efficiency and density were unaffected by variations in polymer molecular weight. Differential scanning calorimetric analysis of the microcapsules showed a lowering of glass transition temperature after microencapsulation. The melting endotherm for phenobarbitone also indicated the presence of crystalline drug in the microcapsule matrix. These microcapsules were found to swell in the aqueous environment and the mean size increased linearly with time. However, the rate of swelling was higher with low molecular weight polymer and also depended on core loading.

Chemical Phenomena↗
PubMedDate not supplied

Biodegradable poly(lactic acid) and poly(lactide-co-glycolide) microcapsules: problems associated with preparative techniques and release properties.

Poly(lactic acid) [PLA] and its co-polymers with glycolic acid [PLCG] have been known to be biodegradable and histocompatible for the past 20 years. Their physico-chemical and biological properties have been found suitable, in many instances, for sustaining drug release in vivo for days or months. Several dosage forms for parenteral administration have been investigated using these polymers and a microencapsulation technique is chosen frequently for its unique properties. There are a limited number of published papers concerning preparation and characterization of PLA or PLCG microcapsules, possibly because of commercial unavailability and difficulties in the synthesis of reproducible batches of these polymers. However, microcapsules can be made using different traditional and non-traditional techniques containing core materials ranging from biological proteins to synthetic drugs. An attempt is made here to review problems associated with the different microencapsulation techniques using PLA or PLCG. In vivo and in vitro drug release from these microcapsules is also reviewed.

Animals↗
PubMedDate not supplied

Microencapsulation using poly(DL-lactic acid). III: Effect of polymer molecular weight on the release kinetics.

Poly(DL-lactic acid) [DL-PLA] microcapsules containing phenobarbitone (PB) were prepared using a w/o emulsion-evaporation method. DL-PLA of three different molecular weights, 20,200, 13,300 and 5,200 were used to prepare microcapsules of nominal core: polymer (C:P) ratios of 1 : 2, 1 : 2.5, 1 : 3 and 1 : 4. The release of PB was investigated in aqueous buffer of pH 2, pH 7 and pH 9 at 37 degrees C and found to follow a square root of time dependent release mechanism. The first order and zero order release mechanisms were disproved by the lower correlation coefficient of the release data as compared to that of the t1/2 mechanism. These microcapsules showed an initial burst phase release followed by a lag phase, during which time little PB was released. This lag time was affected by the polymer molecular weight and pH of the buffer. The polymer matrix was hydrated during the lag phase and a steady state release occurred. The steady state release rate per unit specific surface area (Kh2/SSA) was found to increase exponentially with the increase in core loading of the microcapsules. However the extent of normalized release rate reduced linearly with the increase in polymer molecular weight at any particular core loading (e.g. 20 per cent or 30 per cent). Increases in the normalized steady state release rate with an increase in buffer pH could be correlated to PB solubility in the dissolution medium. PB release from these microcapsules was diffusion controlled. However, swelling and erosion also contributed to the release process.

Delayed-Action Preparations↗
PubMedDate not supplied

Microencapsulation using poly(DL-lactic acid). IV: Effect of storage on the microcapsule characteristics.

Poly (DL-lactic acid) [DL-PLA] microcapsules containing phenobarbitone were prepared using a W/O emulsion method. Microcapsules of nominal C : P ratio, 1 : 2 and 1 : 3 using three different molecular weight polymers, 20,500, 13,300 and 5,200 were investigated to study the effect of storage conditions on the microcapsule properties. All microcapsules were stored under desiccated condition at temperatures of 4 degrees, 20 degrees and 37 degrees C for six months. Storage temperatures of 4 degrees and 20 degrees C did not cause appreciable changes in the release rate after storage. Microcapsules stored at 37 degrees C showed an annealing effect, causing shrinkage of microcapsules, and lowering of the release rate after storage for six months. The microcapsules prepared from low molecular weight DL-PLA fused completely whilst stored at 37 degrees C and the other two high molecular DL-PLA also showed some aggregation. There were insignificant variations in the mean microcapsule diameter during storage. The phenobarbitone content of the microcapsules was also unchanged.

Delayed-Action Preparations↗
PubMedDate not supplied

Microencapsulation using poly (L-lactic acid) II: Preparative variables affecting microcapsule properties.

Poly (L-lactic acid) [L-PLA] microcapsules containing phenobarbitone were prepared from a w/o emulsion system, using light liquid paraffin as the continuum and a solution of phenobarbitone and L-PLA in acetonitrile as the disperse phase. Increasing stirring rate and emulsifying agent concentration were found to reduce microcapsule size. Spans (sorbitan esters of fatty acids) and Brijs (polyoxy ethylene ethers of fatty acids) with different physicochemical properties have been found to produce microcapsules of differing size. An attempt has been made to correlate emulsifier properties and the corresponding microcapsule size. It was found that the emulsifiers had little or no effect on the interfacial tension between light liquid paraffin and acetonitrile and there was no correlation between HLB of the emulsifiers and the resulting microcapsule size. It was postulated that microcapsule size would be affected by the packing of the emulsifier at the interface which would depend on the structure of the emulsifier. Closer, more uniform packing by the straight chain saturated fatty acid containing emulsifiers produced smaller microcapsules than when lose packing, which existed when emulsifiers containing either three fatty acid chains or a 'V' shaped cis-double bond containing fatty acid chain, were used. Microcapsule size was found to increase rapidly with an increase in polymer concentration, if this polymer concentration was increased in conjunction with an increase in the total solid content of the dispersed phase. Increases in polymer concentration by reducing the quantity of solvent for the dispersed phase caused little increase in mean microcapsule size. The phenobarbitone content in the microcapsules was not affected significantly by variations in the preparative parameters.

Chemical Phenomena↗
PubMedDate not supplied

Microencapsulation using poly (L-lactic acid) III: Effect of polymer molecular weight on the microcapsule properties.

Poly (L-lactic acid) microcapsules were prepared using an emulsification and organic solvent evaporation technique (w/o system) with phenobarbitone as a reference core. Three polymers of different molecular weight (61,300; 43,200, 2400), were used to prepare different core loaded microcapsules. Microcapsule size increased with increase in polymer molecular weight. Microcapsule size was also found to increase with increase in core loading with the two high molecular weight polymers, whilst the low molecular weight polymer tended to aggregate to form larger microcapsules than expected. The calculated microcapsule density was found to decrease with an increase in the polymer molecular weight and core loading. 'Encapsulation efficiency' was reduced with the decrease in initial theoretical core loading. However, the phenobarbitone content of the microcapsules was not affected by the difference in polymer molecular weight. Significant morphological differences were observed due to variations in the polymer molecular weight. The two high molecular weight polymers were found to produce non-uniform, porous microcapsules, whilst low molecular weight polymer formed a uniform non-porous surface when core loading was low. With increasing core loading, an increasing number of phenobarbitone crystals were observed on the surface and microcapsules became increasingly porous. This was more evident after release of the drug. Differential scanning calorimetry of the microcapsules showed thermal events for both the polymer and phenobarbitone.

Chemical Phenomena↗
PubMedDate not supplied

Microencapsulation using poly(L-lactic acid) IV: Release properties of microcapsules containing phenobarbitone.

Microcapsules containing phenobarbitone were prepared from poly(L-lactic acid), using a water/oil emulsification and evaporation process. Polymers of three different molecular weights were used. Particle size was found to increase with an increase in core loading and polymer molecular weight. Release studies were carried out at buffer pHs of 2 and 9 at 37 degrees C. The release mechanism was found to follow a square root of time relationship. Almost 90 per cent of the phenobarbitone was released within 2 h. The release rate was not a direct relationship with the phenobarbitone content of the microcapsules because of the differing size and surface area of the microcapsules. However, normalized release rates (release rate/specific surface area) were found to increase linearly with the increase in phenobarbitone content. First order release plots of the data were not found consistent with the core loading. The release at a buffer pH of 9 was very rapid and with some microcapsules was faster than solution of the uncoated crystalline phenobarbitone. At pH 2 release was also very rapid, due to the presence of large pores in the microcapsules of high molecular weight polymers. Release from the microcapsules prepared from low molecular weight polymer was slower than those from high molecular weight polymers. Microcapsules from the low molecular weight polymer were found to swell in the dissolution medium and finally disintegrated into smaller fragments.

Capsules↗