Alendronic acid is one of the most effective diphosphonate compounds used for clinical treatment of bone disorders. It is administered orally as its monosodium salt, for which hydrate and anhydrous crystal forms are known. The monosodium alendronate trihydrate form (NaH 4 A•3H 2 O) is incorporated into medicines as the Active Pharmaceutical Ingredient (API). The NaH 4 A•3H 2 O form can be dehydrated at temperatures above 115 °C, resulting in the anhydrous form (NaH 4 A). Although the crystal structures of both forms have already been reported, an investigation of the reversible dehydration/hydration solid-phase transition is presented here for the first time. A solid-state mechanism for the phase transition, which involves the reversible dehydration−hydration of the NaH 4 A•3H 2 O and NaH 4 A forms, is also proposed. A systematic study comparing the equilibrium solubility and discriminatory intrinsic dissolution of the NaH 4 A•3H 2 O and NaH 4 A forms is included. To achieve this goal, an alternative method of quantifying alendronate anions released from the crystal forms into solution, flame photometry, is proposed and validated. The stability and interconversion of the NaH 4 A•3H 2 O and NaH 4 A forms are probed by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy−attenuated total reflectance (FTIR-ATR), and powder X-ray diffraction (PXRD).

Doxazosin mesylate (DM) is a class II drug in the Biopharmaceutics Classification System (BCS) that is used in several types of hypertension treatments. DM presents almost 20 different polymorphs described in literature/patents, whose existence are usually supported by powder X-ray diffraction (PXRD) data. However, only the crystal form termed as polymorph A (DM-A) and one hydrated DM form present determined crystal structures. Despite its BCS class II classification, there is no preconized DM form for solid oral dosages in pharmaceutical compendia or literature. Also, there are few works comparing the solubility or dissolution rate of DM polymorphs or other solid-state doxazosin forms. This work aimed to describe for the first time the crystal structure of the doxazosin free-base (DB), which was determined here by single-crystal X-ray diffraction. The DB crystal structure was compared to the two known DM crystal structures (DM-A and DM dihydrate) previously determined by PXRD approaches. Additionally, the equilibrium solubility of the DB form was investigated and compared to the two polymorphic DM forms (DM-A and DM-H) in five aqueous media: pure water, 0.01 mol L–1 HCl, and pH 4.5, 5.8, and 7.2 phosphate buffers. Thermal analyses of DB, DM-A, and DM-H were also performed. The DB form had significant solubility only in the HCl medium, but it was less soluble than either DM-A or DM-H. The three forms demonstrated to be practically insoluble in the slightly acid-neutral pH range (pH 5.8 and 7.2 phosphate buffers). DM-A was shown to be more stable (higher melting point) and, consequently, less soluble (from 1.6- to 2-fold) than DM-H. The very low solubility of doxazosin free-base in water demonstrates the need to use its salt multicomponent crystal forms modifications to improve the drug solubility. Additionally, this study suggests DM-A as the polymorph that should be preconized for marketable solid oral dosages containing DM.

This study evaluates various techniques for producing mesalamine (5ASA)-loaded particles employing chitosan as a biopolymer: (1) the polyelectrolyte complexation of chitosan with phthalate hypromelose (HP), (2) the chemical crosslinking of chitosan with genipin and (3) the water-in-oil emulsion method associated with chemical crosslinking with genipin. Systems were characterized by dynamic light scattering, zeta potential (ζ), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR) and a drug release profile. Method (1) was efficiently produced unloaded nanoparticles (491 nm, PdI=0.26 and ζ = 23.2), but the conditions for chitosan and HP cross-linking enhanced the precipitation of 5ASA. Method (2) caused the degradation of the drug. Method 3 produced sub-micron and microparticles, thereby varying the agitation method; 3 h magnetic agitation resulted in 2692 nm, Pdi = 0.6 and ζ = 46, while Ultra-Turrax, 5 min produced submicron particles (537 nm, PdI = 0.6). The percentage yield was approximately 50%, which is very satisfactory considering the impossibility of encapsulating 5ASA using other methods. FTIR showed the covalent interaction of chitosan and genipin. The drug release was rapid in acidic fluid, but in neutral pH a slower release was obtained in the initial stage, followed by rapid release, which may ensure the controlled release of 5ASA in the colon.