Design of Ternary Amorphous Solid Dispersions for Enhanced Dissolution of Drug Combinations.

Using sulfamethoxazole (SMZ) and trimethoprim (TMP) as model drugs, we designed amorphous solid dispersions (ASDs) for the simultaneous solubility enhancement of two active pharmaceutical ingredients (APIs) by exploiting the drug-drug and drug-polymer interactions. In order to make this approach broadly applicable and over a wide dose range, a mixture of SMZ and TMP at weight ratios of 5:1 and 1:5 (w/w) were formulated into ternary ASDs. Depending on the dose ratio of the two drugs, the polymer used was either an aminoalkyl methacrylate copolymer (Eudragit, EDE) or polyacrylic acid.

Dual Functionality of Bile Acid: Physical Stabilization of Drugs in the Amorphous Form and Solubility Enhancement in Solution.

Drugs containing an amino aromatic nitrogen moiety were stabilized in the amorphous form by the surfactant cholic acid (CA). Coamorphous systems of lamotrigine (LAM), pyrimethamine (PYR), and trimethoprim (TRI) were each prepared with CA. Drug-CA interactions, investigated by IR and solid-sate NMR spectroscopy, revealed deprotonation of the carboxylic acid group in CA and the protonation of the most basic nitrogen of the drug.

Phase behavior of poloxamer 188 in frozen aqueous solutions - Influence of processing conditions and cosolutes.

The aim of the study is to investigate the thermal behavior of poloxamer 188 (P188) in binary (P188-water) and ternary (P188-trehalose-water) solutions during freezing and thawing. The thermal behavior of P188 in frozen (binary and ternary) systems was characterized by differential scanning calorimetry (DSC) and low-temperature X-ray powder diffractometry (XPRD) as a complementary technique. The influence of processing conditions (cooling rate, annealing) and a noncrystallizing co-solute (addition of trehalose) on the behavior of P188 was evaluated during freezing as well as thawing.

Formation of Indomethacin-Saccharin Cocrystals during Wet Granulation: Role of Polymeric Excipients.

Formulation of a cocrystal into a solid pharmaceutical dosage form entails numerous processing steps during which there is risk of dissociation. In an effort to reduce the number of unit operations, we have attempted the in situ formation of an indomethacin-saccharin (INDSAC) cocrystal during high-shear wet granulation (HSWG). HSWG of IND (poorly water-soluble drug) and SAC (coformer), with polymers (granulating agents), was carried out using ethanol as the granulation liquid and yielded INDSAC cocrystal granules.

Role of Lattice Disorder in Water-Mediated Dissociation of Pharmaceutical Cocrystal Systems.

Our objective is to mechanistically understand the implications of processing-induced lattice disorder on  the stability of pharmaceutical cocrystals. Caffeine-oxalic acid (CAFOXA) and dicalcium phosphate anhydrate (DCPA) were the model cocrystal (drug) and excipient, respectively. Cocrystal-excipient mixtures were milled for short times (≤2 min) and stored at room temperature (RT)/75% RH.

A supramolecular synthon approach to design amorphous solid dispersions with exceptional physical stability.

A supramolecular synthon approach was exploited to design amorphous solid dispersions (ASDs) of drugs containing an amino aromatic nitrogen moiety and a polyacrylic acid polymer. The interaction between a drug and polymer was confirmed by differential scanning calorimetry, spectroscopy (IR and 15N NMR), and X-ray crystallography. The interaction decreased the molecular mobility, conferred exceptional physical stability and enhanced the drug dissolution.

Solid-State Characterization and Relative Formation Enthalpies To Evaluate Stability of Cocrystals of an Antidiabetic Drug.

The current study integrates formation enthalpy and traditional slurry experiments to quickly assess the physical stability of cocrystal drug substance candidates for their potential to support drug development. Cocrystals of an antidiabetic drug (GKA) with nicotinamide (NMA), vanillic acid (VLA), and ethyl vanillin (EVL) were prepared and characterized by powder X-ray diffractometry (PXRD), spectroscopic, and thermal techniques. The formation enthalpies of the cocrystals, and their physical mixtures (GKA + coformer) were measured by the differential scanning calorimetry (DSC) method reported by Zhang et al.

Mechanistic Insight into Caffeine-Oxalic Cocrystal Dissociation in Formulations: Role of Excipients.

Caffeine-oxalic acid cocrystal, widely reported to be stable under high humidity, dissociated in the presence of numerous pharmaceutical excipients. In cocrystal-excipient binary systems, the water mediated dissociation reaction occurred under pharmaceutically relevant storage conditions. Powder X-ray diffractometry was used to identify the dissociated products obtained as a consequence of coformer-excipient interaction.