Effect of physical and chemical properties on drug release from selected thermosoftening vehicles.
The release profile of several drugs, (chlorpheniramine maleate, salicylic acid, hydrochlorothiazide, p-hydroxy benzoic acid, sulphafurazole, anhydrous theophylline) and the marker (D&C yellow No. 10) was detailed to determine the effect of physical and chemical properties on release from selected thermosoftening matrices (Gelucire 50/02 and 50/13). At a concentration of drug or marker of 2.5% w/w, hydrochlorothiazide showed the slowest release from G50/02, due to its low aqueous solubility, while theophylline showed the highest release owing to its low mol. wt and moderate aqueous solubility. Release reflected two of the selection criteria, aqueous solubility and mol. wt, set forth for the drug/markers used in the study. The hydrophobic matrix, G50/02, offered no enhancement in drug release and functioned in a manner commensurate with other hydrophobic matrices. No hydrogen bonding was noted between any of the drugs or markers and the matrix. As drug or marker concentration increased from 2.5 to 15% w/w, potential hydrogen bonding was noted between p-hydroxy benzoic acid and the matrix. Theophylline no longer had the highest release being replaced by chlorpheniramine maleate and D&C yellow No. 10. With Gelucire excipient G50/13, chlorpheniramine maleate showed the highest release; it dissolved within the matrix at experimental temperature and lowered the matrix melting point. The matrix swelled upon exposure to the dissolution medium and it was from this swollen layer that release occurred. Sulphafurazole, hydrochlorothiazide, salicylic acid and p-hydroxy benzoic acid exerted a similar effect to chlorpheniramine maleate on the matrix. No hydrogen bonding was observed between the drugs and matrix.(ABSTRACT TRUNCATED AT 250 WORDS)
Schering-Plough Research, Kenilworth, NJ 07033.
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D002152:Calorimetry, Differential Scanning; D002744:Chlorpheniramine / Q000737:chemistry; D004058:Diffusion; D016503:Drug Delivery Systems; D005079:Excipients; D005223:Fats; D009821:Oils; D010226:Parabens / Q000737:chemistry; D012459:Salicylates / Q000737:chemistry; D020156:Salicylic Acid; D013696:Temperature; D013806:Theophylline / Q000737:chemistry
D005079:Excipients; D005223:Fats; D009821:Oils; D010226:Parabens; D012459:Salicylates; C071184:Gelucire 50-13; C071183:Gelucire 50-02; D002744:Chlorpheniramine; D013806:Theophylline; C038193:4-hydroxybenzoic acid; D020156:Salicylic Acid