Theophylline Hydrochloride Research Articles

Evaluation of the matrix-forming ability of Chrysophyllum albidum Linn fruit gum in sustained-release tablet formulations

Background: Plant gums are extensively being exploited as pharmaceutical excipients due to the ease of availability, biodegradability, and reduced costs. Aim: This study investigated the application of the fruit gum of Crysophyllum albidum (CFG) as a matrix former in the formulation of chlorpheniramine maleate and theophylline hydrochloride tablets. Materials and Methods: The gum was extracted using acetone and evaluated for flow, swelling, and hydration capacity. Effects of temperature on CFG and drug compatibility were evaluated using differential scanning calorimetry (DSC). Granules containing CFG at 10, 20, and 30% w/w were prepared using the wet granulation method and evaluated for flow properties. Compressed tablets were evaluated for uniformity of weight, hardness, friability, and drug content. In vitro drug release studies were carried out in simulated gastric (pH 1.2) and simulated intestinal (pH 6.8) fluids. Pearson’s similarity correlations were used to analyze results. Results: CFG had a swelling capacity of 22% and hydration capacity of 1.44 with an angle of repose of 30o and Carr’s index of 7.6 signifying good flow. DSC thermogram returned an endothermic glass transition peak at 72.1oC with no appreciable shifts in the peak when CFG was incorporated into the drug. Tablet hardness and friability were concentration dependent with values of 6.5–8.5kg F and 0.04–0.4%, respectively; drug content was within official specifications. Formulations containing 30%w/w CFG sustained drug release for over 12 h and showed better ability to control drug release than HPMC at same concentration. Conclusion: This study shows the propensity of CFG to be used in the formulation of sustained-release tablet formulations.

FORMULATION AND IN-VITRO EVALUATION OF THEOPHYLLINE HYDROCHLORIDE EFFERVESCENT FLOATING TABLETS: EFFECT OF POLYMER CONCENTRATION ON TABLET BUOYANCY

Objective: This study was undertaken to formulate a floating drug delivery system of theophylline hydrochloride using different concentrations of a chosen polymer and then investigate how polymer concentration affects buoyancy and drug release properties of the tablets.
 Methods: Hydroxypropyl methylcellulose (HPMC) at different concentration levels of 15% (F1), 20% (F2) and 30% (F3) was used to form the three formulation batches of floating tablets. Wet granulation method was used for the granule preparation while Sodium bicarbonate and citric acid were used as the gas generating agent. The physical properties of the granules and the floating tablets were evaluated. Also determined were the physicomechanical properties, buoyancy and swelling characteristics of the tablets. The in vitro drug release study was carried out according to the USP I (basket method) for 8h in 900 ml 0.1N HCl at 50 rpm. Samples withdrawn at the regular predetermined time were analyzed spectrophotometrically at a wavelength of 271 nm and data obtained statistically analyzed by one-way analysis of variance (ANOVA). The differences between means were considered significant at P<0.05.
 Results: The result showed that polymer (HPMC) concentration significantly (p>0.05) increased swelling index and improved floating lag time, it had no significant effect on the total floating time. Percentage drug release at the end of 8 h was 100%, 98.2% and 96.13% for formulation F1, F2 and F3, respectively. All three formulations followed the Higuchi drug release kinetics model and the mechanism of drug release was the non Fickian diffusion with exponents of 0.46, 0.51 and 0.56 for the respective batch.
 Conclusion: Batch F3 gave a better-controlled drug release and floating properties in comparison to batch F1 and F2 thus Polymer concentration influenced the onset of floating and controlled the release of Theophylline.

Four salt phases of theophylline

The structures of two anhydrous salt phases of theophylline, namely 1,3-dimethyl-2,6-dioxo-7H-purin-9-ium tetrafluoroborate, C7H9N4O2(+)·BF4(-), and 1,3-dimethyl-2,6-dioxo-7H-purin-9-ium chloride, C7H9N4O2(+)·Cl(-), are reported together with the structures of two monohydrate salt forms, namely 1,3-dimethyl-2,6-dioxo-7H-purin-9-ium chloride monohydrate, C7H9N4O2(+)·Cl(-)·H2O, and 1,3-dimethyl-2,6-dioxo-7H-purin-9-ium bromide monohydrate, C7H9N4O2(+)·Br(-)·H2O. The monohydrate structures are mutually isostructural, with the cations and anions lying on crystallographic mirror planes (Z' = ½). The main intermolecular interaction motif is a hydrogen-bonding network in the same mirror plane. The tetrafluoroborate structure is based on planar hydrogen-bonded theopylline cation dimers; the anions interact with the dimers in a pendant fashion. The anhydrous chloride structure has Z' = 2 and in contrast to the other species it does not form planar hydrogen-bonded constructs, instead one-dimensional chains of cations and anions propagate parallel to the crystallographic c direction. An earlier report claiming to describe an anhydrous structure of theophylline hydrochloride is re-examined in light of these results. It is concluded that the earlier structure has been reported in the wrong space group and that it has been chemically misidentified.

The metabolic fate of 3H-fenetylline in man

The metabolic fate of fenetylline, 7-[2-(α-methylphenethylamino)ethyl] theophylline hydrochloride was studied in four adult male volunteers after oral administration using two tritium-labeled forms, one labeled on the amphetamine and the other on the theophylline moiety. The comparative metabolism of 3H-d-amphetamine sulfate was also investigated. Within four hours after administration the rate of biotransformation of fenetylline ( 3H-amphetamine) to its metabolites, was similar to that obtained with 3H-d-amphetamine. Unchanged amphetamine, hippuric acid and p-hydroxylated amphetamine were identified and quantified for selected periods to 24 hr in the urine of the subjects receiving fenetylline ( 3H-amphetamine) and 3H-d-amphetamine. In subjects administered fenetylline ( 3H-theophylline) the metabolites were quantified and identified as 1,3-dimethyluric acid, 1,3-dimethylxanthine, 1-methyluric acid and 3-methylxanthine. Conclusions based on these metabolic data suggest that fenetylline pharmacologic action may be due primarily to its metabolic degradation to amphetamine and theophylline.

α-ADRENERGIC BLOCKING ACTION OF NOREPHEDRINE-THEOPHYLLINE (NET) OBSERVED IN THE RENAL VASCULAR RESPONSE

Norephedrinetheophylline (NET), l-7[2-(1-methyl-2-hydroxy-2-phenyl-ethylamino)ethyl] theophylline hydrochloride, has molecules of caffeine and ephedrine in its chemical structure as follows: Since diuretic effects of aminoalkyl derivatives of theophylline were investigated by Hildebrandt (1) in 1952, pharmacological properties of these compounds have been elucidated by several workers (2, 3). Among these derivatives, NET was specially studied by Wagenmann and Taugner (4) and Mehmel et al. (5) on its cardiovascular effect. When caffeine and ephedrine are combined to NET, the pharmacological properties are very different from those of caffeine and ephedrine. NET does not show such a marked stimulatory effect on the central nervous system as that of constituents, and its positive chronotropic effect is very slight or converted to the negative one. These observations were attracting the authors' attention to test competition between this compound and catecholamines which seemed likely as a cause of diminution of the cardiovascular effect of this compound. The authors selected the renal vascular bed which is most sensitive to the adrenergic varoconstrictor action and very suitable to test α-adrenergic blocking effect of this compound.

The cerebral hemodynamic response to the xanthine compound, parephyllin (diethyl-aminoethyl theophylline hydrochloride)

A minophylline has been observed to decrease cerebral blood flow in normotensive control subjects, 1 patients with heart failure, 2 and patients with hypertension associated with severe headache. 3 At least in the latter group of patients, the cerebrospinal fluid pressure decrease concurrently with the reduction in cerebral blood flow. Recently a xanthine compound (Parephyllin) (Soluphylline or R-3588) ∗ ∗ Supplied through the courtesy of Riker Laboratories, Inc. has been introduced which has gained widespread use in France 4,5 under the trade name Soluphylline. It produces less gastric irritation than aminophylline and, therefore, it can be given in large doses orally. In addition, it is not irritating by the intramuscular route of administration. Because of these qualities, it seemed worthwhile to study the pharmacodynamics of this drug and to compare it with aminophylline. The current study is concerned with an evaluation of the cerebrovascular hemodynamic response to this compound (Parephyllin).