Biomedical subjects

A T Serajuddin

Publications and source records attributed to A T Serajuddin.

25 records · Page 2Linked to original sources

PubMed1986

Comparative thermal properties of the monohydrates of sodium theophylline and theophylline.

The thermal properties of sodium theophylline monohydrate, as determined by differential scanning calorimetry (DSC), thermogravimetric (TG) analysis and hot stage microscopy, were studied and compared with those of theophylline monohydrate. The onset of dehydration of sodium theophylline monohydrate varied between 170 and 264 degrees C depending on the atmospheric conditions surrounding the sample. Under similar conditions, dehydration of theophylline monohydrate occurred at 18 to 65 degrees C. Sodium theophylline melted with the onset of a DSC endotherm at 391 degrees C. Possible effects of the physicochemical properties of sodium theophylline monohydrate on its dosage forms and the expected superiority of the sodium salt over theophylline and aminophylline are discussed.

Calorimetry, Differential Scanning↗

PubMed1986

Effect of thermal history on the glassy state of indapamide.

The effects of thermal history, e.g. cooling rate, annealing, etc., on the thermal behaviour of indapamide glass were determined by differential scanning calorimetry (DSC). The glass was prepared by heating indapamide crystals (m.p. 162 degrees C) to 180 degrees C, and then cooling the melt to room temperature. The glass transition temperature (Tg) of the material was 98 degrees C. An endotherm, due to thermal relaxation of the glass, was observed in the DSC thermogram when indapamide glass was prepared by slow cooling or was annealed isothermally at a temperature below Tg. Such enthalpy relaxation may be observed during ageing of pharmaceutical glasses and might influence their physico-chemical properties.

Calorimetry, Differential Scanning↗

PubMed1985

Effect of diffusion layer pH and solubility on the dissolution rate of pharmaceutical bases and their hydrochloride salts. I: Phenazopyridine.

The pH-solubility profile of phenazopyridine as determined by the addition of HCl or NaOH solutions to its aqueous suspension was identical to that of its hydrochloride salt except during phase transition from base to salt. With the addition of HCl to a suspension of the base, the pH dropped to a certain point and then remained constant until a supersaturated solution was formed. Only after a high supersaturation did precipitation of the hydrochloride salt occur. The solubility of the salt decreased at low pH due to a common ion effect. Unlike solubility profiles, the pH-intrinsic dissolution rate profiles of the base and its salt differed greatly. At low pH, the dissolution rate of the hydrochloride salt decreased with an increase in HCl concentration, whereas the dissolution rate of the base increased. The self-buffering action of the base and the increase in solubility, leading to a supersaturation of the diffusion layer was responsible for the increase in its dissolution rate with a lowering of the pH of the medium. Good conformity with the Noyes-Whitney equation was demonstrated when the solubility values under pH conditions such that the diffusion layer thickness approaches zero (Cs,h = 0) were used rather than solubilities under pH conditions of the bulk media (Cs). Supersaturation of the dissolution medium was observed during dissolution of the hydrochloride salt at pH 7.

Aminopyridines↗

PubMed1985

Effect of diffusion layer pH and solubility on the dissolution rate of pharmaceutical acids and their sodium salts. II: Salicylic acid, theophylline, and benzoic acid.

The pH-solubility profiles of salicylic acid and theophylline, as determined by the addition of HCl or NaOH to their aqueous suspensions, were identical with those of their sodium salts except during phase transitions from acid to salt or vice versa. Supersaturated solutions were formed during phase transitions. Unlike the solubility profiles, the pH-intrinsic dissolution rate profiles of an acid and its salt differed greatly. Good conformity with the Noyes-Whitney equation was demonstrated when the solubility values under pH conditions as the diffusion layer thickness, h, approaches zero (Cs,h = 0) were used rather than solubilities under pH conditions of the bulk media (Cs). The pH when h approaches zero (pHh = 0) was estimated by equilibration of a dissolution medium with an excess of material. Good correlation was shown between the pHh = 0 values of benzoic acid estimated according to this method and the pHh = 0 values reported in the literature. The intrinsic dissolution rate constant, the ratio of the diffusion coefficient to the diffusion layer thickness (D/h), may be assumed constant when comparing the dissolution rates of salicylic acid, theophylline and sodium theophylline. On the other hand, D/h decreased significantly during dissolution of sodium salicylate due to a large increase in Cs,h = 0 and the consequent increase in viscosity in the diffusion layer. A simple method of predicting the dissolution rate of an acid or a salt at different pH values has been developed.

Acids↗

PubMed1984

pH-Solubility profile of papaverine hydrochloride and its relationship to the dissolution rate of sustained-release pellets.

The pH-solubility profile of papaverine hydrochloride (I) was determined using the phase-solubility technique and equilibrium solubilities in buffers. The release of I from sustained-release pellets consisting of a shellac-based matrix was determined by the USP basket technique and was found to exhibit zero-order kinetics. Release rates at various pH values of the permeating solvent were compared with the pH-solubility profile and were directly proportional to the solubility below, but not above, the apparent pHmax (3.9). This lack of proportionality was also shown by the intrinsic dissolution rates. The effect was attributed to the self-buffering action of I and the metastability of the papaverine salt-base system in the vicinity of pHmax. It is postulated that the outer layer of polymer and filler on the surface of the pellets forms a barrier which determines the rate of release. The inner matrix serves as a drug reservoir in which the internal pH may not be the same as the bulk pH.

Buffers↗

PubMedDate not supplied

Solid-state NMR and IR for the analysis of pharmaceutical solids: polymorphs of fosinopril sodium.

The two polymorphic modifications of fosinopril sodium have been characterized as to their differences in melting behaviour, powder X-ray diffraction patterns, Fourier transform infrared spectra (FTIR), and solid-state 31P- and 13C-NMR spectra. The polymorphs were found to be enantiotropically related based upon melting point, heat of fusion, and solution mediated transformation data. Analysis of the solid-state FTIR and 13C-NMR data indicated that the environment of the acetal side chain of fosinopril sodium differed in two polymorphs, and that there might be cis-trans isomerization about the C6-N peptide bond. These conformational differences are postulated as the origin of the observed polymorphism.

Crystallization↗

PubMedDate not supplied

Moisture sorption behavior of selected bulking agents used in lyophilized products.

To develop a rational approach for the formulation of lyophilized products, six bulking agents commonly used in freeze-dried formulations were lyophilized under identical conditions, and their moisture sorption behavior, before and after lyophilization, were determined as a function of relative humidity at 25 degrees C. The bulking agents evaluated were mannitol, anhydrous lactose, sucrose, D(+)-trehalose, dextran 40 and povidone (PVP K24). The materials were also characterized for their crystal and thermal properties by powder X-ray diffraction, DSC and TG after exposure to various relative humidity conditions. Mannitol was crystalline and non-hygroscopic both before and after lyophilization with total moisture contents of 0.1 to 0.3% w/w between 10 and 60% RH. Anhydrous lactose, sucrose and trehalose were crystalline prior to lyophilization with moisture contents of 0.86, 0.15 and 9.2%, respectively, and the crystalline materials were relatively non-hygroscopic. Upon lyophilization, they converted to the amorphous form and had moisture contents of 1.6, 2.5 and 1.2%, respectively. The amorphous materials sorbed moisture rapidly upon exposure to increasing relative humidity conditions. The amorphous lactose converted to its crystalline hydrate form at 55% RH after sorption of an additional 10% moisture. This conversion to the crystalline hydrate form was accompanied by desorption of practically all the moisture sorbed by the amorphous form. Similarly, lyophilized sucrose converted to its crystalline form after the sorption of additional 4.5% moisture at 50% RH, and the lyophilized trehalose sorbed additional 10% moisture prior to its conversion to a crystalline hydrate form at 50% RH. Dextran and povidone were amorphous and hygroscopic both before and after lyophilization and they sorbed as much as 10-20% moisture at 50% RH. It is well established that different drugs, especially proteins, need different levels of moisture for optimal stability. The results of the present study show that moisture contents of lyophilized cakes may be varied and optimized by the selection of suitable excipients.

Calorimetry, Differential Scanning↗