Investigation of in-vitro release characteristics of NSAID-loaded polylactic acid microspheres.

The intra-pulmonary delivery of non-steroidal anti-inflammatory drug-loaded PLA microspheres has potential utility in the treatment of inflammatory lung conditions such as asthma. Drug encapsulation efficiency and release kinetics depend upon a variety of parameters in the production process, all of which affect the properties of the microspheres produced. The release of piroxicam from PLA microspheres followed an apparently biphasic release profile. PLA microspheres containing indomethacin, however, exhibited kinetics which approached more closely to zero order release. The effect of microsphere production parameters upon these release profiles has been investigated. Results indicate that factors affecting the nature of the microsphere matrix have the greatest influence on release profiles. The use of halothane as organic solvent in the microsphere production increases the burst release effect. Residual halothane is known to be present in the microspheres, producing a less stable matrix, thus allowing much faster release of the drug. The nature of drug incorporated also appears to affect the nature of the microspheres matrix. Piroxicam-loaded microspheres possess a much more porous matrix than indomethacin-loaded microspheres, as evidenced by washing procedures. This difference could explain the difference in release profiles between the two types of microspheres.

Poly-(D,L-lactic acid) microspheres incorporating histological dyes for intra-pulmonary histopathological investigations.

Polylactic acid (PLA) microspheres incorporating fluorescein as a histological marker have been prepared and used as a model for the testing of inhaled PLA microspheres (2-5 microns) in the lung. PLA microspheres (20 mg) were delivered to rabbits in the form of a saline nebulization. The distribution pattern within the pulmonary system showed that the fluorescein-labelled microspheres were distributed about the four lobes in discrete groups. The comparative numbers of these groups showed a trend towards a reduced concentration in the lower lobes. Subsequent histological examination revealed that the microsphere-treated lungs had been significantly damaged after 24 h. Histological damage was assessed in terms of pulmonary haemorrhage, eosinophilia and neutrophil infiltration.

Influence of pH on the release of propranolol hydrochloride from matrices containing hydroxypropylmethylcellulose K4M and carbopol 974.

The dissolution of propranolol hydrochloride from matrices containing hydroxypropylmethylcellulose K4M (HPMC K4M) and carbopol 974 has been investigated using 0.1 M hydrochloric acid or phosphate buffer at pH 4.5 or pH 7.5. In 0.1 M hydrochloric acid, HPMC K4M predominantly controlled release since carbopol has a low solubility at this pH. As the pH increased, the carbopol became increasingly ionized and interacted with propranolol hydrochloride to form an insoluble complex which retarded the release of the drug. In addition, the nature of the interaction between carbopol 974 and HPMC K4M altered. DSC and viscometric studies indicated that the two polymers contributed synergistically to the gel network at pH 7.5. Thus at pH 7.5 polymers contributed to matrix integrity and to the control of drug release.

Soluble asparaginase-dextran conjugates show increased circulatory persistence and lowered antigen reactivity.

Oxidized dextrans of increasing molecular weight were bound covalently to Erwinia carotovora asparaginase. The resulting conjugates retained 50% of their enzyme activity and showed marked resistance to proteolysis by trypsin and chymotrypsin and inactivation by asparaginase-specific antibody. When tested in-vivo, the larger molecular weight conjugates showed prolonged circulatory survival in both immune and non-immune animals and failed to elicit full type III hypersensitivity or anaphylactic reactions when injected into sensitized guinea-pigs. Rabbits could tolerate multiple doses of the asparaginase conjugate without developing an immunity to the enzyme. A conjugate showing increased circulatory half-life and lowered antigen reactivity should have therapeutic potential.

The effect of incorporation of indomethacin with polyethylene glycol 6000 in a solid dispersion on its in vivo properties in the rat.

Preparations of indomethacin and indomethacin in combination with PEG 6000 were administered in solid form by the oral route to male rats. No significant differences in anti-oedema activity were observed between the different preparations of indomethacin, but high blood levels of drug were observed following dosing with indomethacin, in a PEG 6000 melt. Rapid dispersion formulations of indomethacin were also found to be gastro-toxic.

Prostaglandins and the anti-inflammatory activities of aspirin and sodium salicylate.

Acetylsalicylic acid (aspirin) and sodium salicylate are equally effective in reducing the swelling in the carrageenan-induced paw test and the accumulation of leucocytes into the inflammatory exudate produced by the subcutaneous implantation of polyvinyl sponges in the rat. Aspirin but not sodium salicylate caused a significant reduction in the potentiation of paw oedema found after the concurrent administration of carrageenan and arachidonic acid. Some implications of these findings are discussed.