ABSTRACT
An acid-insoluble, methacrylic acid, methyl methacrylate copolymer (Eudragit L-100) was used to give an enteric coating to a grass pollen extract in order to protect it against gastric degradation. Substantial protection against the degradative effects of simulated gastric secretion was demonstrated using this preparation which was well tolerated by grass pollen-allergic volunteers. The enteric-coated allergen induced a greater secondary antibody response than did an aqueous presentation when administered orally to guinea pigs which had been primed previously by subcutaneous injection. This result indicates that an effective hyposensitisation regimen could consist of a short series of initial parenteral injections, followed by an oral course of the protected allergen.
Subject(s)
Desensitization, Immunologic/methods , Immune Tolerance/drug effects , Pollen/immunology , Polymethacrylic Acids , Tablets, Enteric-Coated , Acrylic Resins/pharmacology , Administration, Oral , Adult , Animals , Antibody Formation/drug effects , Drug Stability , Gastric Acid/physiology , Guinea Pigs , Humans , Injections, Subcutaneous , Isoelectric Focusing , Pollen/analysis , Radioallergosorbent Test , Tablets, Enteric-Coated/analysis , TemperatureABSTRACT
The Sartorius absorption simulator was used as a device to detect possible in vivo gastrointestinal tract drug interactions. The drugs chosen were propranolol hydrochloride and two diuretics (namely hydrochlorothiazide and frusemide) commonly used in conjunction with propranolol hydrochloride for the treatment of hypertension. The results show that the presence of both diuretics increased the intestinal absorption rate constant and the percentage diffused of propranolol hydrochloride. Moreover, the presence of propranolol hydrochloride also caused the intestinal absorption rate constants and the percentages diffused of both diuretics to be increased.
Subject(s)
Furosemide , Hydrochlorothiazide , Propranolol/metabolism , Drug Combinations , Drug Interactions , Intestinal Absorption/drug effects , Models, BiologicalABSTRACT
The apparent partition coefficient (Kapp.) of propranolol hydrochloride alone and in the presence of hydrochlorothiazide and frusemide were determined between chloroform and artificial intestinal juice. Both diuretics significantly reduced the relatively high Kapp. of propranolol hydrochloride. On the other hand, the relatively low Kapp. of both diuretics were significantly increased by the presence of propranolol hydrochloride. Also in vitro solubility studies were carried out using the Sartorius solubility simulator. The frequently prescribed therapeutic combination of propranolol hydrochloride tablets and either hydrochlorothiazide or frusemide tablets seems, on the whole to have similar in vitro solubility patterns when compared to those of the individual drugs. However, the mutual effects on the apparent partition coefficient revealed in the present work can be one of the factors responsible for improving the in vitro absorption of propranolol hydrochloride and the diuretics when present together.
Subject(s)
Furosemide , Hydrochlorothiazide , Propranolol , Chemistry, Pharmaceutical , Drug Interactions , Propranolol/administration & dosage , Solubility , Tablets , Time FactorsABSTRACT
A unidirectional transport condition is often assumed when studying the in vitro diffusion of drugs. The present work describes a kinetic model that can be applied to beyond the first diffusion period. Acetylsalicylic acid was chosen as a model substance and its in vitro diffusion was studied using the Sartorius absorption simulator. The results of the two kinetic models (unidirectional and bidirectional) were in good agreement with each other. The curvature of the corrected substance concentration in the artificial plasma versus time plot can be used as a warning signal to detect passage beyond the first diffusion period.