The objects of this investigation were (i) to prepare and characterize a new anhydrous theophylline phase that is metastable under ambient conditions, and (ii) to prepare model tablet formulations containing either this metastable anhydrate (I*) or stable anhydrous theophylline (I), store them under different relative humidity (RH) conditions, and compare their dissolution behavior. I* was prepared by dehydration of theophylline monohydrate (II). Variable temperature X-ray powder diffractometry of II revealed the following series of transitions: II-->I*-->I. The metastable anhydrate, I*, which has not yet been reported in the literature, appears to be related monotropically to I. It was characterized by ambient and variable temperature X-ray powder diffractometry, Karl Fischer titrimetry, and thermoanalytical techniques (differential scanning calorimetry and thermogravimetric analysis). Tablet formulations containing either I* or I were prepared and stored at 33 and 52% RH (room temperature). The solid state of the drug was monitored by X-ray powder diffractometry and the tablets were subjected to the USP dissolution test. In tablets, I* completely converted to I in < or = 10 days when stored at either 33 or 52% RH. Scanning electron microscopy provided direct visual evidence of recrystallization. This recrystallization was accompanied by a decrease in the dissolution rate of the stored formulations that was so pronounced in the formulations stored at 52% RH that they failed the USP dissolution test. The in situ solid-state transition appears to be responsible for the decrease in dissolution rate observed following storage. Stored tablets containing I showed neither a phase transition nor an alteration in their dissolution behavior.

SymposiumGlucagon is currently approved for the treatment of severe hypoglycemia.1,2 Because glucagon is not stable in aqueous solutions, these preparations are provided as lyophilized powders for reconstitution. Once reconstituted, these preparations begin to degrade and fibrillate rapidly and must be discarded if not used immediately. While suitable for treatment of severe hypoglycemia, these glucagon preparations are unstable and thus not suitable for development of additional indications including minidosing for mild to moderate hypoglycemia 3 and infusion pump applications. In particular, a stable glucagon suitable for use in infusion pump systems creates an opportunity for treatment of hypoglycemia under different conditions, including as a component of an artificial or "bionic" pancreas system. 4,5Despite a vigorous research effort, to date development of aqueous-based glucagon formulations (without reconstitution) has failed to produce any clinical candidates. We have developed a novel, nonaqueous glucagon formulation based on a biocompatible pharmaceutical solvent, dimethyl sulfoxide, which demonstrates excellent physical and chemical stability (up to 2 years at room temperature) 6 at relatively high concentrations.The solubility and stability of this formulation allow for development of a higher concentration formulation (5 mg/ml vs 1 mg/ml for the currently approved glucagon formulations) to facilitate administration from devices such as autoinjectors, pens, pumps, and so on. Furthermore, this glucagon formulation is in clinical development as a treatment for severe hypoglycemia 6 and moderate hypoglycemia and for management of blood glucose in pump applications.This article presents stability, compatibility, and preclinical data supporting progression of this formulation into clinical development. Background: Despite a vigorous research effort, to date, the development of systems that achieve glucagon stability in aqueous formulations (without reconstitution) has failed to produce any clinical candidates. We have developed a novel, nonaqueous glucagon formulation based on a biocompatible pharmaceutical solvent, dimethyl sulfoxide, which demonstrates excellent physical and chemical stability at relatively high concentrations and at high temperatures.

No abstract

Pharmaceutical solids are able to exist in several forms: polymorphic crystalline and amorphous arrangements. They present differences in their physico-chemical properties, for instance, melting point, density, morphology, solubility and color. These characteristics may have an impact on the stability (physical and chemical), bioavailability and bioequivalence1; e.g. amorphous substances are unstable than crystalline substances. Differences in degrees of drug crystallization affect chemical and physical stability, rather than crystalline polymorphism of the substance. Ciprofloxacin is a broad-spectrum antiinfective agent of the fluoroquinolone class. Ciprofloxacin has in vitro activity against a wide range of gram-negative and gram-positive microorganisms. Microcrystalline cellulose had been reported as an adhitive for ciprofloxacine tablets, following the pharmaceutical procedures of mixing and pressing. The next work develops an amorphous fraction quantification analysis performing the Rietveld method in mixtures of the active pharmaceutical ingredient ciprofloxacin (API-Cipro) and microcrystalline cellulose (MC) in different concentrations (100%CIP, 100% MC, 90%CIP-10%MC, 75%CIP-25%MC, and 50%CIP-50% MC). Ciprofloxacin and microcrystalline cellulose were refined applying the Rietveld method taking into account the microstructure parameters only. The instrumental parameters were obtained using LaB6 as reference standard. The background of the diffraction patterns were modeled as a contribution of: (i) Thermal Diffuse Scattering (TDS) of the present crystalline phases; (ii) Air scattering. The X-ray powder diffraction pattern (XRD) was recorded at room temperature in a Bruker X Ray diffractometer model D8 Discover with the Debye-Scherrer and Brag-Brenteno geometry, determine the impact in the absorption effect. [1] Norman Chieng, Thomas Rades, Jaakko Aaltonen. An overview of recent studies on the analysis of pharmaceutical polymorphs, Journal of Pharmaceutical and Biomedical Analysis 55 (2011) 618-644