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Crystal polymorphism of pharmaceuticals has well-known profound effects on the physical, chemical, and pharmaceutical properties of drugs, which can result in changes in the solubility, stability, dissolution, bioavailability, and efficacy of drugs. In this review article, famotidine (FAM), which has a well-known trade name of Pepcid®, was selected as a model drug. Although FAM has three polymorphs (forms A, B and C), forms A and B have been commonly discussed. The active pharmaceutical ingredient (API) in the commercial version of FAM is the metastable form B. FAM has been a concern of FDA because of the physical properties, solubilities, bioavailabilities, or bioequivalencies of the different polymorphic forms. In addition, a patent infringement suit of FAM polymorph had been made sound legal arguments in the pharmaceutical market. We review the solid-state characteristics, thermodynamics, polymorphic transformation, and quality control of FAM in drug products. In particular, pharmaceutical processes, such as grinding, compression, and heating temperature have a significant effect on the polymorphic transformation of FAM. Moreover, environmental humidity and residual water content should be well controlled to prevent polymorphic transformation of FAM during pharmaceutical processing. Several thermal and spectroscopic analytical techniques used for qualitative and quantitative determinations of polymorphic transformation of FAM after different treatments or quality control of FAM in the commercial tablets before and after the expiration dates have been discussed.

Purpose. To investigate the suitability of hydrophilic or hydrophobia membranes for use as potential thermo-responsive drug delivery system.

Sodium diclofenac enteric-coated microcapsules were prepared by a spray-drying technique with Eudragit L 30D as enteric-coating material. The spray-dried powder, mixed with neocel or flo-starch, or the mixture of neocel and flo-starch (weight ratio, 1:1) was directly compressed into a tablet. The micromeritic properties of the spray-dried powder and the mixed powder for tableting were investigated. The flowability of the spray-dried powder was poor but improved after incorporating the excipients. The release rates of sodium diclofenac from the spray-dried powder, the mixed powder before tableting, and the tablets were determined in 0.1 N HCl solution, pH 6.8, phosphate buffer solution, distilled water, and pH-changed medium. The results indicated that the spray-dried powder, the mixed powder before tableting, and the tablets all exhibited enteric-coated release properties; these powders and tablets showed some resistance to stimulated gastric acid and then released drug more rapidly in pH 6.8 buffer solution. The weight ratio of neocel to flo-starch plays an important role in controlling the release of sodium diclofenac from enteric tablets. The 1:1 weight ratio of neocel to flo-starch was more suitable for designing the microdispersed sodium diclofenac enteric-coated tablets.

The use of plasticizers to affect the properties of drug-free, self-adhesive Eudragit E-100 films with higher transparency was tested for possible transdermal drug delivery. Triacetin was found to be an effective first plasticizer for Eudragit E-100 polymer. In order to improve the flexibility and adhesiveness of Eudragit E-100 film plasticized with triacetin, a more flexible and adhesive, secondary plasticizer was added. Plasticizer–polymer compatibility was evaluated by measuring transparency, surface topography, and solubility. Secondary plasticizers with a low molecular weight and a solubility parameter similar to that of Eudragit E-100 polymer and triacetin were compatible. Further, a lower molecular weight or higher concentration of the secondary plasticizers might lead to greater plasticizing action, reduce tensile strength, and increase film elongation, independent of the hydrophilicity of the plasticizer. The adhesive strength of Eudragit E-100 film under a 180° peel test was also affected by the molecular weight and solubility parameter of the secondary plasticizers used. The results indicate that PEG 200, propylene glycol, diethyl phthalate, and oleic acid can serve as a secondary plasticizer to improve the transparency, flexibility, and adhesion of Eudragit E-100 film.

Enalapril may undergo the thermal-induced intramolecular interaction to cause an enalapril diketopiperazine (DKP) formation. It is interesting to study the influence of Eudragit E, as a coating polymer, on the stability of enalapril maleate. The reaction kinetics of the solid-state degradation process of pure enalapril maleate and Eudragit E/enalapril maleate mixture with different weight ratios were examined. The mechanism of solid-state interaction between Eudragit E and enalapril maleate was also discussed.The cast samples of pure enalapril maleate or Eudragit E/enalapril maleate mixture after evaporating the solvent were prepared on an aluminum foil and also determined by reflectance Fourier transform infrared (FTIR) microspectroscopy equipped with thermal analyzer.The result indicates that the interaction might occur between enalapril maleate and Eudragit E in the solid state after evaporating the solvent. The thermal-dependent FTIR spectra show that not only the formation of DKP but also the six-membered cyclic anhydride occurred in the enalapril maleate/Eudragit E mixture in the heating process. Two pathways for solid-sate interaction were proposed. The stability of enalapril maleate was dependent on the weight ratio of enalapril maleate and Eudragit E. The activation energy (n = 3) of DKP formation for pure enalapril maleate was about 141.2+/-0.7 kJ/mol, but it was reduced significantly to 86.7+/-0.8 kJ/mol after interaction with Eudragit E (weight ratio: 1:1), suggesting Eudragit E might exacerbate the degradation of enalapril maleate. However, the degradation accelerated by Eudragit E was reduced in high content of Eudragit E.When the weight ratio of both components was 1:1, Eudragit E might interact with the carboxyl group of maleic acid to exacerbate the degradation of enalapril maleate. However, the excess amount of Eudragit E might somewhat reduce the degradation of enalapril, due to the interaction that occurred between Eudragit E and carboxyl group of enalapril.

The processes of dehydration, rehydration, and solidification of trehalose dihydrate were examined to simulate it in the drying and wetting states.Techniques included differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and Fourier transform infrared (FT-IR) microspectroscopy combined with thermal analysis. Trehalose dihydrate was pressed on one KBr pellet (IKBr method) or sealed within two KBr pellets (2KBr method) for FT-IR measurement.On the DSC thermogram, the shoulder between 60 degrees C and 80 degrees C represented a transitional change because no weight loss occurred in this area of the TGA curve. The endothermic peak at 100 degrees C represented dehydration of trehalose dihydrate to anhydrous trehalose; a 9.5% weight loss in the TGA curve occurred from 81 degrees C. The thermal-dependent FT-IR spectra for trehalose dihydrate prepared by the IKBr method changed markedly with temperature in the 1800-1500 cm(-1) region during dehydration. IR peak intensity at 1687 cm(-1) assigned to the bending vibrational mode of solid-like water declined with temperature and decreased sharply at 67 degrees C. Another IR peak at 1640 cm(-1) associated with the bending of liquid water increased at 67 degrees C but disappeared at 79 degrees C as a result of water evaporation. Both peaks for the sample prepared by the 2KBr method changed dramatically at 64 degrees C; peak intensity at 1640 cm(-1) remained constant above 64 degrees C.A new polymorphic transition of trehalose dihydrate was first evidenced at 64-67 degrees C from both DSC curves and thermal-related FT-IR spectra. This transitional temperature reflected the thermal-dependent transformation from solid-like water to liquid water in the trehalose dihydrate structure during dehydration. During rehydration, trehalose anhydrate was rehydrated to the dihydrate, and liquid water in the dihydrate structure was again transformed to solid-like water. The polymorphic transition within this temperature range seems to correlate with the bioprotective effect of trehalose dihydrate in preserving protein stability.