Solubility Partition Coefficient Research Articles

Amide Codrug Approach: Synthesis and Biopharmaceutical Evaluation of Nonsteroidal Anti-Inflammatory Drug and Calcium Channel Blocker Conjugates

Background and Aim Geriatric patients often suffer from osteoarthritis and hypertension comorbidity. The codrugs approach was shown to be an effective strategy for targeting diseases synergistically hence improving the quality of life of patients. The present study aimed to synthesize various Nonsteroidal Anti-inflammatory Drugs NSAIDs and Calcium channel blocker CCB Co-drugs and biopharmaceutical study to eliminate the adverse gastrointestinal effects of the NSAIDs to treat comorbid conditions in geriatric patients with significant reduction of polypharmacy.Methods Various conjugates were synthesized by a one-pot amidation reaction of Amlodipine with various NSAIDs. Further characterization by melting point TLC Fourier transform infrared nuclear magnetic resonance and mass spectroscopy followed by solubility partition coefficient and hydrolysis study in SGF and SIF.Results The synthesized codrugs satisfied the structural criteria of the proposed plan. From the biopharmaceutical and hydrolysis study it was observed that the co-drugs underwent significant hydrolysis in SIF pH 7.4 and have showed delayed onset of action with respect to the standard drugs. The delayed onset may be due to the hydrolysis of amide linkage followed by the release of the prodrug which finally releases the active drug.Conclusion The findings illuminated the codrugs pros and cons aiding optimization and development. This research advances amide-based mutual prodrugs and their use in pharmaceutical research. The outcome of this exploration confirmed that the described co-drug can offer desirable safety and therapeutic benefits. Hence these conjugates could be considered for further development.

596. Steam distillation of taints from cream: I. Theoretical considerations and properties of the reference substances, diacetyl and acetoin

The rate of removal of a dissolved tainting substance from cream by steam-distillation treatment is dependent in part on the relative volatility (or boiling point) of the pure substance, in part on the temperature of steam distillation, and in part on the influence of water on the vapour pressure of the tainting substance in dilute solution (i.e. on the activity coefficient, γ).The application of Raoult's law and Henry's law to the problem of removal of taints from cream is discussed. For the dilute solutions commonly encountered in cream Henry's law can be expected to apply.The equilibrium relationships for diacetyl and acetoin used as reference substances in investigations on cream-deodorizing equipment have been determined. The equilibrium coefficient for diacetyl in water at concentrations up to 50 p.p.m. in the liquid, as measured by the continuous equilibrium vaporization method, is 39·3. With rise in concentration above 50 p.p.m. in the liquid the coefficient decreases. At 100 p.p.m. it is 32 and at 1000 p.p.m. it is 20. The coefficient for acetoin in water at all concentrations up to 1·2% in the liquid is constant at 1·29. The activity coefficient for diacetyl in concentrations up to 50 p.p.m. was found to be 26·4 and for acetoin at concentrations up to 1·2%, 5·4.For diacetyl the solubility partition coefficient as between butterfat and water rises from 0·47 at 100° F. to 0·74 at 180° F. For acetoin the partition coefficient remains constant at 0·18–0·19 over this range of temperatures. Correspondingly diacetyl is removed equally easily from butterfat and from water, whereas acetoin steam-distils much more readily from butterfat than from water.