Release Theophylline Formulation Research Articles

Spectroscopic-Based Chemometric Models for Quantifying Low Levels of Solid-State Transitions in Extended Release Theophylline Formulations

Variations in the solid state form of a pharmaceutical solid have profound impact on the product quality and clinical performance. Quantitative models that allow rapid and accurate determination of polymorphic changes in pharmaceutical products are essential in ensuring product quality throughout its lifecycle. This study reports the development and validation of chemometric models of Raman and near infrared spectroscopy (NIR) for quantifying the extent of pseudopolymorphic transitions of theophylline in extended release formulations. The chemometric models were developed using sample matrices consisting of the commonly used excipients and at the ratios in commercially available products. A combination of scatter removal (multiplicative signal correction and standard normal variate) and derivatization (Savitzky-Golay second derivative) algorithm were used for data pretreatment. Partial least squares and principal component regression models were developed and their performance assessed. Diagnostic statistics such as the root mean square error, correlation coefficient, bias and Q2 were used as parameters to test the model fit and performance. The models developed had a good fit and performance as shown by the values of the diagnostic statistics. The model diagnostic statistics were similar for MSC-SG and SNV-SG treated spectra. Similarly, PLSR and PCR models had comparable performance. Raman chemometric models were slightly better than their corresponding NIR model. The Raman and NIR chemometric models developed had good accuracy and precision as demonstrated by closeness of the predicted values for the independent observations to the actual TMO content hence the developed models can serve as useful tools in quantifying and controlling solid state transitions in extended release theophylline products.

Use of dika fat in the formulation of sustained release theophylline tablets and capsules

Sustained release theophylline tablets and capsules were prepared with dika fat, a solid vegetable oil extracted from the kernels of Irvingia gabonesis var gabonesis and var excelsia. Anhydrous theophylline was incorporated into dika fat by the fusion method. The in vitro release of the theophylline was monitored by the so-called half change dissolution method in stimulated gastric juice USP without pepsin and in stimulated intestinal juice without pancreatin, respectively. The USP XX paddle method was used. A level of sustained release was achieved over a 6-h period in both the tabletted and encapsulated dosage forms. The theophylline formulations containing dika fat, prepared in this study, exhibited dissolution profiles similar to those of Theo 24, Theodur and Respid, some commercial sustained release theophylline formulations.

Effect of once daily and twice daily sustained release theophylline formulations on daytime variation of bronchial hyperresponsiveness in asthmatic patients.

BACKGROUND: Previous studies evaluating spirometric values and symptoms have shown that once daily theophylline administered in the evening produces greater stabilisation of the airway function in asthmatic patients than the...

Xanthan Gum and Alginate Based Controlled Release Theophylline Formulations

The oral absorption of theophylline from two sustained release formulations, formulated using xanthan gum or sodium alginate, has been investigated in the beagle dog. A commercial product was used for comparison. Dissolution tests and an in vivo dog study both indicated that the xanthan gum tablet released drug at a constant rate and performed as a pH independent zero-order controlled release formulation. With the alginate tablet, faster dissolution rates were observed when acid medium was present. The pH dependent release behavior of the alginate formulation is explained. Drug release mechanisms which are influenced by the gel behaviors in these two polymers are discussed. The relative oral bioavailabilities of these two formulations in dog were 74–84% compared to immediately releasing capsules, and three-fold that of the commercial product with an equivalent dose.

Sustained release theophylline preparations. Practical recommendations for prescribing and therapeutic drug monitoring.

Theophylline is an important antiasthmatic medication which has bronchodilator properties. With increased understanding of the relationships of serum theophylline concentration and effect, both adverse and beneficial, oral dosage forms were developed to provide consistent serum theophylline concentrations with the benefit of convenient dosage intervals for long term use. Since factors such as concurrent disease states, drug interactions and age have a profound effect on theophylline disposition, relatively sophisticated dosage guidelines have evolved. Theophylline is in fact a model drug for the application of pharmacokinetic principles to the individualization of a treatment regimen. The purpose of this discussion is to review the relationship of serum theophylline concentration and pharmacodynamic effect and the special properties of oral sustained release theophylline formulations, and to provide a practical approach to prescribing theophylline. Guidelines are provided on the use of serum theophylline concentrations to individualize the theophylline dose, with an analysis of available techniques to monitor theophylline.

Comparison of Sustained Release Theophylline Formulations

Comparison of Sustained Release Theophylline Formulations

Plasma theophylline concentrations in patients with chronic obstructive airways disease after administration of a new sustained release theophylline formulation.

British Journal of Clinical PharmacologyVolume 13, Issue 4 p. 569-571 Free Access Plasma theophylline concentrations in patients with chronic obstructive airways disease after administration of a new sustained release theophylline formulation. DR Taylor, DR TaylorSearch for more papers by this authorCD Kinney, CD KinneySearch for more papers by this authorDG McDevitt, DG McDevittSearch for more papers by this author DR Taylor, DR TaylorSearch for more papers by this authorCD Kinney, CD KinneySearch for more papers by this authorDG McDevitt, DG McDevittSearch for more papers by this author First published: April 1982 https://doi.org/10.1111/j.1365-2125.1982.tb01423.xCitations: 3AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat REFERENCES JENNE, J.W., WYZE, E., ROOD, F.S. & McDONALD, F.M. (1972). Pharmacokinetics of theophylline. Clin. Pharmac. Ther., 13, 349– 360. LEAHEY, W.J. & KELLY, J.G. (1976). Measurement of theophylline in plasma by high performance liquid chromatography. Br. J. clin. Pharmac., 3, 947. McDEVITT, D.G., ELWOOD, R.K. & RUSSELL, C.J. (1979). Why measure plasma theophylline concentrations Curr. Med. Res. Opin., 6, Suppl 6, 26– 34. MITENKO, P.A. & OGILVIE, R.I. (1973). Rational intravenous doses of theophylline. New Engl. J. Med., 289, 600– 603. OGILVIE, R.I. (1978). Clinical pharmacokinetics of theophylline. Clin. Pharmacokin., 3, 267– 293. PIAFSKY, K.M. & OGILVIE, R.I. (1975). Dosage of theophylline in bronchial asthma. New Engl. J. Med., 292, 1218– 1222. RUSSELL, C.J., ELWOOD, R.K., KINNEY, C. & McDEVITT, D.G. (1980). Plasma theophylline concentrations following administration of microcrystalline theophylline and a new sustained release theophylline preparation to normal subjects. Eur. J. clin. Pharmac., 18, 351– 354. Citing Literature Volume13, Issue4April 1982Pages 569-571 ReferencesRelatedInformation

Components of variability in serum theophylline concentrations during maintenance therapy with a sustained release formulation.

Fifteen adult chronic asthmatic patients were studied on 6 consecutive days of the second week of treatment with a new sustained release theophylline formulation, and 8 were again studied after three months on the same dosing regimen (375 mg b.i.d.). Serum theophylline concentrations were maintained in the therapeutic range (peak - 19.7 +/- 5.0 micrograms/ml; trough - 13.0 +/- 3.2 micrograms/ml) throughout the 12 hour dosing interval, and were greater than 75% of the peak concentration over 8.6 +/- 2.9 h. A degree of drug accumulation was evident in that the 1-h and 5-h levels rose from 12.2 +/- 4.1 and 4.5 +/- 4.8 micrograms/ml during the second week to 16.9 +/- 4.6 and 18.4 +/- 4.5 micrograms/ml, respectively, at three months. Between-patient differences accounted for 61%-71% of the total variation in steady state theophylline concentrations. After accounting for differences due to sampling time and assay error, unexplained random, within-individual variability amounted to 11%-18% of the total. Quantitative estimation of these components of variability may be incorporated into dosage forecasting methods based on single determinations of serum concentration.

PROCEEDINGS OF THE AUSTRALASIAN SOCIETY OF CLINICAL AND EXPERIMENTAL PHARMACOLOGISTS

PROCEEDINGS OF THE AUSTRALASIAN SOCIETY OF CLINICAL AND EXPERIMENTAL PHARMACOLOGISTS

Serum level monitoring of a new slow release theophylline formulation in patients with chronic lung disease.

1 Serum theophylline levels were performed in 26 patients with chronic lung disease receiving rapid release theophylline (125 mg 6 hourly) and 28 patients receiving slow release theophylline (250 mg 12 hourly) under steady state conditions. 2 For rapid release theophylline the mean +/- s.d. serum theophylline levels at 0 and 2 h were 41.0 +/- 21.7 and 52.3 +/- 20.9 mumol l-1 respectively and for slow release theophylline at 0, 4 and 6 h 43.7 +/- 25.5, 50.9 +/- 23.0 and 51.7 +/- 26.4 mumol l-1 respectively. 3 Serum theophylline monitoring with slow release theophylline was performed in 70 patients with chronic lung disease. The initial dose was 250 mg administered 12 hourly. 4 The mean +/- s.d. steady state serum theophylline level achieved was 76.0 +/- 18.8 mumol l-1 and the mean +/- s.d. dose to produce this level was 9.4 +/ 2.3 mg kg-1 day-1. There was no correlation between dosage and serum theophylline level. 5 Sixty percent of patients required a dosage change for stabilization (375 to 1000 mg/day). Seventeen patients reported unwanted effects (nausea or tremor), which either settled quickly or resolved with dosage reduction. 6 Serum theophylline levels were obtained at different dosages in 44 patients and 18 patients demonstrated dose-dependent kinetics. 7 An initial dose of 500 mg/day is recommended and dosage increments should not exceed 125 mg/day with monitoring by serum theophylline levels.

Evaluation of a new sustained release theophylline formulation by the measurements of salivary levels of the drug in humans.

Dry agar beads containing theophylline were prepared. The release rate of theophylline from the agar beads in vitro was smaller than the dissolution rate of the drug from pure drug powders. The salivary levels of the drug following oral administration of the agar beads to three healthy volunteers were determined by reversed-phase high pressure liquid chromatography. Results of pharmacokinetic analyses indicated sustained absorption of the drug following the administration of the agar beads.