Estimation of intramolecular cyclization activation energies via isothermal gravimetric analysis: a technical note.
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Antihypertensive Agents↗
Biomedical subjects
Yung-Chi Lee
Publications and source records attributed to Yung-Chi Lee.
The protective effect of lactose on lyophilization of CNK-20402.
The goal of this research was to assess the feasibility of using lyophilization to stabilize an exploratory compound, CNK-20402, with a minimal amount of impurity (CNK-20193) formation. A mixed-level full factorial experimental design was used to screen excipients of glycine, mannitol, lactose monohydrate, and povidone K-12. Cryostage microscopy, powder x-ray diffraction, Karl Fischer titration, HPLC, and water vapor sorption were used to assess the formulations' physicochemical properties and stability. Initial physical characterization from powder x-ray diffraction revealed that the mannitol- and glycine-containing formulations were crystalline with the patterns of the pure excipient, whereas the remaining formulations were amorphous in structure. Chemically, the formulations stored at 50 degrees C for 1 month had 2.36%, 1.05%, 0.81%, 0.79%, and 0.49% CNK-20193 for glycine, mannitol, drug alone, povidone K-12, and lactose formulations, respectively. The formulations containing drug-mannitol, drug alone, and drug-lactose were selected for accelerated stability study based on statistical analysis. Recovery of CNK-20193 in these formulations was 1.22%, 1.00%, and 0.55%, respectively, when stored at 40 degrees C/75% relative humidity storage conditions for 3 months. Water vapor sorption analysis revealed weight gains of over 7%, 21%, and 24% for the mannitol, lactose, and drug alone formulations, respectively. Testing formulations with different concentrations of lactose by water vapor sorption indicated that CNK-20402 concentrations as low as 10% (wt/wt) could inhibit the recrystallization of lactose. The lactose-containing formulation exhibited the best stability among the formulations tested. The protective mechanism of lactose on the CNK-20402, based on water vapor sorption studies, is believed to be a result of (1) the drug-lactose interaction, and (2) competition between lactose and drug for the residual water in the formulation.
Chemistry, Pharmaceutical↗
An intravenous formulation decision tree for discovery compound formulation development.
Discovery and pre-clinical animal efficacy assessment formulation development efforts are challenged by limited compound availability and stringent timelines. The implementation and use of a systematic discovery formulation scheme can facilitate this important process. We observed that nearly 85% of Pfizer, Ann Arbor discovery compounds (n>300) submitted for discovery and pre-clinical injectable formulation development in the year 2000 could be formulated by pH adjustment, cosolvent addition, or a combination of the two approaches. Based on the vehicle data generated by this laboratory, a discovery formulation decision tree, that utilizes the solubilization approaches described above, is proposed. The proposed decision tree can be adapted and modified by pharmaceutical scientists to conform to best practices put forth by their institutions for discovery animal studies requiring injectable dosage forms.
Buffers↗
Review on the systemic delivery of insulin via the ocular route.
Systemic drug absorption from the ocular route is well known. Although there is some absorption from the conjunctival sac, the nasal meatus is the site where the majority of systemic absorption of instilled drug takes place. This article reviews the principles of systemic absorption of insulin applied topically to the eye. The physiological and pharmaceutical considerations for formulation development and the strategy of improving the systemic absorption and bioavailability of insulin are also discussed.
Administration, Topical↗