Modifying the diffusion layer of soluble salts of poorly soluble basic drugs to improve dissolution performance.
The dissolution mechanism of soluble salts of poorly soluble bases can be complex because both the dissolution of the salt and precipitation of the free base can occur depending on the experimental conditions and properties of the molecule. The dissolution of three soluble salts of poorly soluble bases is described in this paper. Two of these compounds precipitate as free base under normal stomach pH conditions (pH from 2-4) during dissolution. This free base precipitation is a result of formation of free base on the surface of the dissolving salt. Diffusion Layer modulated (DLM) solids are defined and presented that can effectively counteract this precipitation mechanism. These DLM materials employ excipients in order to modify the pH or solubility conditions at the surface of the dissolving salt to minimize precipitation of the free base that can occur. Rotating disk dissolution data is presented which shows how these formulated solids can act to improve the dissolution profile for these materials.
Hawley
Michael
M
Pfizer Inc., Eastern Point Road, Groton, CT 06340, USA. michael.hawley@pfizer.com
Morozowich
Walter
W
D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001682:Biological Availability; D002491:Central Nervous System Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D011232:Chemical Precipitation; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D020008:Delavirdine / Q000008:administration & dosage / Q000493:pharmacokinetics; D004058:Diffusion; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008954:Models, Biological; D010879:Piperazines / Q000008:administration & dosage / Q000493:pharmacokinetics; D033362:Powder Diffraction; D012492:Salts / Q000008:administration & dosage / Q000493:pharmacokinetics; D012995:Solubility; D013449:Sulfonamides / Q000008:administration & dosage / Q000493:pharmacokinetics; D000096926:Benzenesulfonamides
D000998:Antiviral Agents; D002491:Central Nervous System Agents; D020008:Delavirdine; D010879:Piperazines; D012492:Salts; D013449:Sulfonamides; C100448:sonepiprazole; D000096926:Benzenesulfonamides