Modulating the dehydration conditions of adefovir dipivoxil dihydrate to obtain different physical forms of anhydrate.

The physical form of anhydrous adefovir dipivoxil (AD), obtained following the dehydration of AD dihydrate, was governed by the kinetics of water removal. The rate and extent of water removal following the dehydration of AD dihydrate was manipulated by altering the sample size, pan configuration, and heating rate in a differential scanning calorimeter. Interestingly, when there was moderate resistance to water removal, a new anhydrous polymorph (melting point 80°C) was obtained.

Mechanism of amorphous itraconazole stabilization in polymer solid dispersions: role of molecular mobility.

Physical instability of amorphous solid dispersions can be a major impediment to their widespread use. We characterized the molecular mobility in amorphous solid dispersions of itraconazole (ITZ) with each polyvinylpyrrolidone (PVP) and hydroxypropylmethylcellulose acetate succinate (HPMCAS) with the goal of investigating the correlation between molecular mobility and physical stability. Dielectric spectra showed two mobility modes: α-relaxation at temperatures above the glass transition temperature (Tg) and β-relaxation in the sub-Tg range.

Molecular motions in sucrose-PVP and sucrose-sorbitol dispersions-II. Implications of annealing on secondary relaxations.

Purpose: To determine the effect of annealing on the two secondary relaxations in amorphous sucrose and in sucrose solid dispersions.

Methods: Sucrose was co-lyophilized with either PVP or sorbitol, annealed for different time periods and analyzed by dielectric spectroscopy.

Results: In an earlier investigation, we had documented the effect of PVP and sorbitol on the primary and the two secondary relaxations in amorphous sucrose solid dispersions (1).

Controlling the physical form of mannitol in freeze-dried systems.

A potential drawback with the use of mannitol as a bulking agent is its existence as mannitol hemihydrate (MHH; C₆H₁₄O₆·0.5H₂O) in the lyophile. Once formed during freeze-drying, MHH dehydration may require secondary drying under aggressive conditions which can be detrimental to the stability of thermolabile components.

Correlation between molecular mobility and physical stability of amorphous itraconazole.

The goal was to investigate the correlation between molecular mobility and physical stability in amorphous itraconazole and identify the specific mobility mode responsible for its instability. The molecular mobility of amorphous itraconazole, in the glassy as well as the supercooled liquid state, was comprehensively characterized using dynamic dielectric spectroscopy. Isothermal frequency sweeps in the 5-40 °C temperature range revealed a β-relaxation which exhibited Arrhenius temperature dependence.

Molecular mobility as a predictor of the water sorption by annealed amorphous trehalose.

Purpose: The work aims at investigating the correlation of water sorption potential with different measures of molecular mobility in an annealed amorphous model compound (trehalose).

Methods: Amorphous trehalose, prepared by freeze-drying, was annealed at 100°C (17°C < T (g)) for up to 120 h. Global molecular mobility was studied using a broadband dielectric spectrometer in the frequency range of 10(6)-10(-2) Hz.

Molecular mobility as an effective predictor of the physical stability of amorphous trehalose.

Amorphous trehalose was prepared by different methods, viz., freeze-drying, spray-drying and dehydration of trehalose dihydrate. The different molecular relaxations were characterized by dynamic dielectric spectroscopy.

Use of dielectric spectroscopy to monitor molecular mobility in glassy and supercooled trehalose.

Dielectric spectroscopy was used to comprehensively characterize the molecular mobility in amorphous trehalose, an extensively used bioprotective agent. Isothermal frequency sweeps were carried out at different temperatures in the glassy and supercooled liquid states of freeze-dried trehalose. Two previously reported secondary relaxations were observed at temperatures far below its glass transition temperature (T(g)).

Subtraction of DC conductivity and annealing: approaches to identify Johari-Goldstein relaxation in amorphous trehalose.

Amorphous trehalose finds extensive use as a stabilizer of biomolecules including proteins and phospholipids. Hypothesizing that molecular mobility is a determinant of its stability, dynamic dielectric spectroscopy (DDS) was used to map the different modes of mobility. Isothermal dielectric relaxation profiles of amorphous trehalose were obtained, over the frequency range of 10(-1)-10(7) Hz, and at temperatures ranging from 30-170 °C.

Monitoring phase transformations in intact tablets of trehalose by FT-Raman spectroscopy.

The purpose of this study is to monitor phase transformations in intact trehalose tablets using FT-Raman spectroscopy. Tablets of trehalose dihydrate, amorphous trehalose (obtained by freeze-drying aqueous trehalose solutions), and anhydrous trehalose (beta-trehalose) were prepared. The tablets were exposed to different conditions [11% and 0% RH (60 degrees C); 75% RH (25 degrees C)] and monitored periodically over 96 h using Raman spectroscopy.

Is relief from diabetes just a breath away?

Pulmonary insulin delivery is steadily emerging as a promising solution for the treatment of diabetes mellitus. The large as well as thin absorptive area of the lungs has not been explored until now for the treatment of systemic disease like diabetes. With an understanding of the lung anatomy and physiology and the transport mechanism of insulin through lungs, diabetic treatment through the pulmonary route may well become the reality of the 21(st) century.

Study of forced degradation behavior of enalapril maleate by LC and LC-MS and development of a validated stability-indicating assay method.

In the present study, comprehensive stress testing of enalapril maleate was carried out according to ICH guideline Q1A(R2). The drug was subjected to acid (0.1N HCl), neutral and alkaline (0.