Pahala Simamora

Solubilization of rapamycin.

The solubilization of rapamycin, a poorly water soluble investigational immunosuppressive drug, by facilitated hydrotropy is presented. Partially water-miscible aromatic solutes (such as benzyl alcohol, benzoate, or benzoic acid) can be solubilized by water-miscible cosolvents, such as ethanol and propylene glycol. Once solubilized, the partially miscible aromatic solute becomes a solubilizing agent. This technique yielded a dramatic (>1000-fold) increase in the aqueous solubility of rapamycin.

Aquafac: Aqueous Functional Group Activity Coefficients

Abstract AQUAFAC, a new group contribution method for estimating aqueous activity coefficients, has been applied to a large set of organic compounds. The current work introduces 27 new group values for hydrocarbon, halogen, and non-hydrogen bond donating oxygen groups. Group values (q-values) have been derived from a data set of 621 compounds representing over 1700 individual solubility values. No correction factors were used in generating the current group values. AQUAFAC was found to give acceptable results when applied to some environmentally important compounds.

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.

Unified physical property estimation relationships (upper)

Abstract A scheme is presented to evaluate twenty-one molecular properties using known theoretical and semi-empirical equations with geometric descriptors and group contribution values. The geometric descriptors and group contribution values which are derived strictly from molecular structure will be described along with the various physical property calculations. This will allow all twenty-one properties to be estimated from only the structure of the compound.

Controlled delivery of pilocarpine. 2. In-vivo evaluation of Gelfoam® device

Abstract In this report, an ocular device for the controlled delivery of pilocarpine was evaluated in albino rabbits using miosis as a bioassay for efficacy. The device was fabricated using Gelfoam® (absorbable gelatin sponge, USP) in the form of a matrix system. The efficacy of the device was compared in a cross-over study to the two conventional ophthalmic pilocarpine dosage forms, the eyedrop and the gel. The in-vivo results show that the gelfoam device is more effective than the two conventional pilocarpine dosage forms in prolonging the duration of the pilocarpine activity.

Quantitative Structure Property Relationship in the Prediction of Melting Point and Boiling Point of Rigid Non-Hydrogen Bonding Organic Molecules

Abstract Simple techniques to predict the melting point (T m ) and boiling point (T b ) of non-hydrogen bonding rigid molecules have been developed. The compounds used include halogen, methyl, cyano, and nitro derivatives of benzene and polycyclic compounds. Melting point prediction uses additive constitutive properties e.g., molecular fragments and a non-additive non-constitutive property, molecular symmetry. Boiling point estimation employs only additive constitutive properties. It was found that symmetry affects the entropy of melting which in turn affects the melting point.

Precipitation of pH solubilized phenytoin

Abstract Precipitation of phenytoin often occurs as it is diluted by blood after intravenous injection. The presence and the amount of precipitate depend upon the initial pH and buffer capacity of the formulation vehicle. The prediction of phenytoin precipitation can be carried out in vitro using isotonic Sorensens phosphate buffer (SPB) to simulate blood. An equation is developed to calculate the change in solubility resulting from the change in pH due to dilution. This equation is very difficult to solve analytically because it involves a high order polynomial. However, it can be solved numerically using a spreadsheet program. The relationship between pH or solubility and dilution can then be presented graphically. Therefore, the precipitation of any pH solubilized drug due to dilution under various conditions can be easily predicted. This is illustrated for several aqueous phenytoin solutions.

Upper II: Calculation of physical properties of the chlorobenzenes

Abstract The twelve chlorobenzenes are used to evaluate the previously described UPPER scheme. Twenty-one physical properties are calculated strictly from molecular structure with no adjustable or fitted parameters and compared with experimental values. The UPPER scheme does reasonably well with estimating all of the considered properties.