Sustained-release Theophylline Research Articles

A Smart Hydrogel from Salvia spinosa Seeds: pH Responsiveness, On-off Switching, Sustained Drug Release, and Transit Detection.

The use of synthetic and semi-synthetic materials in drug delivery systems has associated drawbacks like costly synthesis, toxicity, and biocompatibility issues. Therefore, there is a need to introduce novel materials to overcome such issues. Naturally occurring and water-swellable polysaccharides are advantageous in overcoming the above-mentioned issues. Therefore, we are reporting a novel hydrogel (SSH) isolated from the seeds of Salvia spinosa as a sustained release material. SSH was explored for its pH-dependent and salt-responsive swelling before and after compression in a tablet form. Stimuli-responsive swelling and deswelling were also monitored at pH 7.4 and pH 1.2 in deionized water (DW) and normal saline and DW and ethanol. The sustained-release potential of SSH-based tablets was monitored at gastrointestinal tract (GIT) pH. The transit of SSH tablets was ascertained through an X-ray study. The swelling of SSH in powder and tablet form was found in the order of DW > pH 7.4 > pH 6.8 > pH 1.2. An inverse relation was found between the swelling of SSH and the concentration of the salt solution. The SSH showed stimuli-responsive swelling and de-swelling before and after compression, indicating the unaltered nature of SSH even in a closely packed form, i.e., tablets. Sustained release of theophylline (< 80%) was witnessed at pH 6.8 and 7.4 during the 12 h study following zeroorder kinetics, and radiographic images also showed 9 h retention in GIT. These investigations showed the potential of SSH as a pH-sensitive material for sustained and targeted drug delivery.

Effects of combination treatment with theophylline sustained release tablets and thymalfasin on pulmonary function, immunity, and inflammation in elderly patients with chronic obstructive pulmonary disease and respiratory failure

Purpose: To investigate the effect of combined administration of theophylline sustained-release tablets and thymalfasin on pulmonary function, immunity, and inflammation in elderly patients with chronic obstructive pulmonary disease (COPD) and respiratory failure.&#x0D; Methods: A total of 122 elderly patients in Fujian Geriatric Hospital, Fuzhou, China who suffered from acute attack of COPD with respiratory failure from January 2019 - January 2020 were selected for this study. The patients were divided randomly and evenly into study and control groups. Theophylline sustained-release tablets were administered to subjects in the control group, while theophylline sustained-release tablets and thymalfasin were administered to subjects in the study group. Pulmonary function indicators, viz, forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC), blood gas indicators (PaCO2, PaO2, and SaO2), inflammatory factors (sICAM-1, PGE2, and hs-CRP), immune cells (Th17, Treg, and Th17/Treg), as well as exercise ability (the 6 min walking distance test) were evaluated for each group. Adverse reactions were also assessed.&#x0D; Results: There were no significant differences in pulmonary function, blood gas, inflammation, immunity, and exercise ability between the two groups before treatment (p &lt; 0.01). However, all parameters improved significantly for both groups after treatment, with better outcomes for all parameters in the study group. A proportion of (14.75 %) patients in the study group showed adverse events, while 13.11 % of the patients in the control group exhibited adverse effects, meaning that the study group had a slightly but not significantly higher rate of adverse events.&#x0D; Conclusion: The combined administration of theophylline sustained-release tablets and thymalfasin reduces inflammation and improves physical immunity, leading to enhancement of blood gas and pulmonary function in elderly patients with COPD and respiratory failure. However, further clinical trials are required prior to application of this combination therapy in clinical practice.

Sustained Release Theophylline (SRT): An Older Drug for COPD which Still Retains its Edge in the Management of this Chronic Disease

Sustained release theophylline (SRT) has been an important component in the Pharmacotherapy of Chronic Obstructive Pulmonary Disease (COPD). Recent years have witnessed a dynamic change in the treatment of this disease. Several new drugs, especially inhaled ones, have largely supplanted the oral drugs used in COPD. SRT has also been relegated to such a position that it is an option which may be used in very severe cases only on the Clinician’s discretion. The axiom that development of new drugs does not belittle the clinical edge of the previous used one is in our opinion applicable to SRT. In this abstract, we attempt to underline the importance of Sustained-Released Theophylline (SRT) in the management of COPD.The endeavour is to systematically emphasize the myriad actions of SRT which provide relief by multiple means to patients in Acute exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD).

Formulation and evaluation of theophylline sustained release matrix tablets using synthetic polymers

The aim of present work was to develop theophylline sustained release tablets which could improve patient compliance towards the effective management of asthma The polymers, HPMC (Hydroxy propyl methyl cellulose) K4M, HPMC K100M, Eudragit, Chitosan in blending and granulation stage of processing and evaluate their physico-chemical properties. The precompression limits of the powder blends used for the preparation of sustained-release tablets were in an acceptable range of pharmacopeial specification with excellent flow and good compressibility. Wet granulation method prepared tablets using different grades of polymers HPMC K100, HPMC K4M, Eudragit, Chitosan. The active ingredient, release retardants, diluents, fraction of polymer are mixed to make wet mass for granulation. The in- vitro release was prolonged to 12 hours using HPMC K4M, HPMC K100M, Chitosan, Eudragit. F9 formulation prolonged the theophylline release in 12 hours. The effect of polymer on drug release was studied. Thus, sustained release matrix tablets can promise better patient compliance through reduction in over-all dose and dosage regimen, which can be of excessive support to treat chronic disease.

In vivo Evaluation of Theophylline Sustained Release Matrix Tablets Containing Low Viscosity Guar Gum

The present investigation was carried out to evaluate the utility of guar gum as a hydrophilic matrix carrier in the design of oral controlled drug delivery. Based on the earlier reports, the low viscosity guar gum appears to be superior to medium and high viscosity grades of guar gum in providing a sustained delivery of theophylline along the GI tract. Conducting in vivo studies on theophylline matrix tablets containing 10% of low viscosity guar gum as a representative formulation assessed the in vivo performance of the guar gum matrix tablets. The in vivo studies were carried out in dogs. The effective concentration of theophylline was sustained for a period of 16 hours. The extended tmax, reduced absorption rate constant, prolonged MRT, unchanged Cmax and unchanged bioavailability indicate a controlled release of theophylline from the guar gum matrix tablets resulting in a sustained absorption and prolonged blood levels of theophylline. The theophylline matrix tablets showed blood levels well below 15 ?g/mL indicating freedom from adverse effects. Based on the studies, guar gum appears to be a potential carrier in the design of oral controlled drug delivery systems.

Sustained-release Theophylline Matrix Tablet Using Hydrophilic Polymers: Effects of Agitation Rates and pH on Release Kinetics

Background and Objective: Modified-release tablet of theophylline that can increase its usefulness despite narrow therapeutic index and short half-life, is being formulated. However, the rate and extent of release of a sustained-release delivery system can be affected by some factors. This work is aimed at investigating the effect of agitation rates and pH of dissolution medium on release kinetics of sustained-release theophylline tablet formulated using hydrophilic polymers.&#x0D; Materials and Methods: Theophylline granules was formulated using 3 polymers (HPMC, SCMC and Sodium alginate) to form 3 batches of granule by wet granulation method, using 95% ethanol. The granules compacted to batches of sustained-release matrix tablets. The tablet batches were characterized for tablet properties, and dissolution studies carried out using simulated gastric and intestinal fluid separately at different agitation rates. The data from dissolution studies were subsequently fitted into 4 drug release kinetics models.&#x0D; Results: The swelling of the 3 polymers over time was noteworthy, although there was no significant difference between them. The release kinetic followed the Higuchi model and zero-order releasing more than 90% over 8 hours period, with t10 and t90 released at 14 minutes and 6.8 hours respectively. The mechanical properties of the tablets were within the acceptable limit.&#x0D; Conclusion: The agitation rate and pH of the medium had no significant effect on the release of the theophylline from the batches of matrix tablets except in the case of F1 which showed a marginally significant effect.

Development and Optimisation of Novel Polymeric Compositions for Sustained Release Theophylline Caplets (PrintCap) via FDM 3D Printing

This study reports a thorough investigation combining hot-melt extrusion technology (HME) and a low-cost fused deposition modelling (FDM) 3D printer as a continuous fabrication process for a sustained release drug delivery system. The successful implementation of such an approach presented herein allows local hospitals to manufacture their own medical and pharmaceutical products on-site according to their patients’ needs. This will help save time from waiting for suitable products to be manufactured off-site or using traditional manufacturing processes. The filaments were produced by optimising various compositions of pharmaceutical-grade polymers, such as hydroxypropyl cellulose (HPC), Eudragit® (RL PO), and polyethylene glycol (PEG), whereas theophylline was used as a model thermally stable drug. For the purpose of the study, twin-screw hot-melt extrusion (HME) was implemented from the view that it would result in the formation of solid dispersion of drug in the polymeric carrier matrices by means of high shear mixing inside the heated barrel. Four filament compositions consisting of different ratios of polymers were produced and their properties were assessed. The mechanical characterisation of the filaments revealed quite robust properties of the filaments suitable for FDM 3D printing of caplets (PrintCap), whereas the solid-state analyses conducted via DSC and XRD showed amorphous nature of the crystalline drug dispersed in the polymeric matrices. Moreover, the surface analysis conducted via SEM showed a smooth surface of the produced filaments as well as caplets where no drug crystals were visible. The in vitro drug release study showed a sustained release profile over 10 h where about 80% of the drug was released from the printed dosage forms. This indicates that our optimised 3D printed caplets could be suitable for the development of sustained release on-demand drug delivery systems.

Formulation and in-vitro evaluation of theophylline sustained release tablet

The aim of present study was to prepare sustained release tablet of Theophylline so as to prolong its elimination time and at the same time to keep cost of the formulation minimum. In this study ethyl cellulose and Eudragit are used in the formulation to sustain the release of Theophylline. Ethyl cellulose and Eudragit are added at the granulation step to form a sustained release coating around each granule. Different batches were designed one after another on trial and error basis to get the optimum drug release upto 12 hours.&#x0D; Keywords: Theophylline, ethyl cellulose, Eudragit, sustained release, coating, tablet.

A systematic review of second-line controller combination therapy options for the management of asthma

First-line controller combination therapy for the management of asthma is a low-dose inhaled corticosteroid (LD-ICS) + a long-acting β-agonist (LABA), and second-line options are a LD-ICS + a leukotriene receptor antagonist (LTRA), LD-ICS + sustained-release theophylline (SR-T), and a medium-/high-dose ICS (HD-ICS). The purpose of this review is to assess the various second-line combination therapy options for the management of asthma. We systematically reviewed randomized controlled trials (RCTs) in adult patients with asthma, extracting and synthesizing data from eligible articles on study design, duration, randomization, blinding, withdrawal, run-in period, type of analysis, and names and doses of drugs. The primary outcome measure was change in percentage predicted forced expiratory volume in 1 second (% FEV1), and the secondary outcome was frequency of asthma exacerbations. Nine RCTs (three blinded and six open-label trials) were selected for the review. One study investigated LD-ICS + LTRA compared with HD-ICS, two studies investigated LD-ICS + SR-T compared with HD-ICS, and five studies investigated LD-ICS + LTRA compared with LD-ICS + SR-T. Only one of the nine RCTs compared all treatment options as mentioned in Global Initiative for Asthma (GINA) guidelines. Seven RCTs examined the primary outcome (change in % FEV1). No significant difference was observed (four RCTs; % FEV1) between LD-ICS + LTRA and LD-ICS + SR-T, but one RCT reported better clinical improvement with LD-ICS + LTRA than with LD-ICS + SR-T (% FEV1). Likewise, similar clinical effects (two RCTs) were observed between LD-ICS + SR-T and HD-ICS, one based on % FEV1 and the other based on exacerbation improvement. One RCT concluded that LD-ICS + LTRA was an effective and well-tolerated alternative to HD-ICS (exacerbation improvement). LD-ICS + LTRA resulted in greater clinical improvement when comparing all second-line treatment options in one RCT (% FEV1 and exacerbation improvement). All nine studies had a high risk of bias according to a modified Cochrane risk-of-bias tool for quality assessment of RCTs. Existing RCTs provide low-quality evidence of the superiority of second-line controller options for asthma management. This systematic review recommends that clinically relevant, stringently designed RCTs with appropriate sample sizes and durations are conducted to identify the best second-line controller option.

Observation of the Improvement in Nocturnal Asthma Symptoms with Administration of Once Daily Sustained Released Theophylline

Objective: The aims and objective of this study to observe the improvement in Nocturnal Asthma symptoms and Quality of Life (QoL) with administration of once daily sustained release theophylline preparation.Background: Nocturnal symptoms are a common part of the asthma. Nocturnal asthma is defined by a drop in forced expiratory volume in 1 second (FEV1) of at least 15% between bedtime and awakening in patients with clinical and physiologic evidence of asthma, which may include improvement in QoL.Methodology: The patient with Chronic Persistent Asthma, both sex, age &gt;18 to 50 years of age and preferably patients with nocturnal exacerbations were included in the study. All patients were diagnosed on the basis of clinical history, physical examination, chest X-ray and pulmonary function tests, in accordance with the clinical criteria for the diagnosis by the GINA. The recruitment period was between March 2017 and August 2017 Shaheed Suhrawardy Medical College Hospital, Dhaka.Results: It was observed that 65(92.85%) was found exacerbation free night and 5(7.15%) patients were found exacerbation with sustained release Theophylline. There are significantly improved qualities of life between 1st follow up to 2nd follow up, 3rd follow up and 4th follow up p&lt;0.001 which was statistically significant. Spirometry test was gradually improved between 1st visit of FEV1 to 2nd, 3rd and 4th visit of FEV1, (p&lt;0.001) that was statistically significant.Conclusion: Most of the patients were found exacerbation free night. There are significantly improved quality of life between 1st follow up to 2nd follow up, 3rd follow up and 4th follow up in Spirometry test. The value of FEV1 was gradually improve in the lst visit, 2nd, 3rd and 4th visit with sustained release Theophylline.J Shaheed Suhrawardy Med Coll, December 2017, Vol.9(2); 74-77

Clinical and economic impact of a one-year treatment with omalizumab in patients with severe allergic asthma within a drug programme in Poland

BackgroundAllergic asthma is the most prevalent phenotype of severe asthma where treatment with omalizumab (OMB) has been proven to be particularly beneficial. In Poland, OMB therapy is available and reimbursed within a drug programme where strict inclusion and exclusion criteria are defined.The objective of this study was to present a descriptive analysis regarding the trends in outcomes (clinical, quality of life, costs) among a cohort of patients who satisfy inclusion criteria for the initiation of OMB treatment and who successfully responded to OMB according to a set of objective criteria.MethodsA retrospective analysis of data collected during the 52 weeks of OMB treatment was carried out. The study population was adolescents and adults with severe allergic asthma that was uncontrolled despite a combination of high-dose inhaled corticosteroids (ICS)/long-acting beta-agonists (LABA) and/or other controllers (leukotriene receptor antagonists (LTRA), sustained-release theophylline, and short- or long-acting muscarinic antagonists (SAMA/LAMA), who were the first to finish the one-year treatment. A clinical and cost analysis for patients included in the programme was conducted comparing the one-year pre-treatment period to the one-year treatment period outcomes.ResultsData of 85 patients who completed the first year of therapy were reviewed and analysed. Add-on OMB treatment resulted in a median decrease in exacerbation rate of 66% relative to the baseline and a reduction in oral steroid (OCS) dose by an average of 7.7 mg. At the end of the 52 weeks of therapy the changes in the quality of life questionnaire (AQLQ) and the asthma control questionnaire (ACQ) scores were 1.86 and 1.45 points, respectively. The mean cost of asthma treatment increased by an average of 15,979 EUR per patient per year (baseline period – 802 EUR/patient/year; OMB treatment – 16,781 EUR/patient/year). The cost to avoid one exacerbation was 17721 EUR.ConclusionThe clinical outcomes for the observed subset of patients were highly improved. At the same time, costs of the treatment increased, mainly due to the high OMB costs. Other costs associated with a lower number of hospitalizations and ED and office visits and a reduction in OCS dose decreased. These descriptive data can be used for further investigation in defining patients who benefit the most from OMB treatment in clinical practice.

Formulation development and process analysis of drug-loaded filaments manufactured via hot-melt extrusion for 3D-printing of medicines

Three dimensional(3D)-printing via fused deposition modeling (FDM) allows the production of individualized solid dosage forms. However, for bringing this benefit to the patient, active pharmaceutical ingredient (API)-loaded filaments of pharmaceutical grade excipients are necessary as feedstock and have to be produced industrially. As large-scale production of API-loaded filaments has not been described in literature, this study presents a development of 3D-printable filaments, which can continuously be produced via hot-melt extrusion. Further, a combination of testing methods for mechanical resilience of filaments was applied to improve the prediction of their printability. Eudragit RL was chosen as a sustained release polymer and theophylline (30%) as thermally stable model drug. Stearic acid (7%) and polyethylene glycol 4000 (10%), were evaluated as suitable plasticizers for producing 3D-printable filaments. The two formulations were printed into solid dosage forms and analyzed regarding their dissolution profiles. This revealed that stearic acid maintained sustained release properties of the matrix whereas polyethylene glycol 4000 did not. Analysis of the continuous extrusion process was done using a design of experiments. It showed that powder feed rate and speed of the stretching device used after extrusion predominantly determine the diameter of the filament and thereby the mechanical resilience of a filament.

Hydro-alcoholic media effects on theophylline release from sesamum polysaccharide gum matrices

Concomitant ingestion of alcohol and medications can greatly affect drug plasma concentrations as dose dumping or failure may occur as a result of the fact that formulation excipients may not always be resistant to alcohol. In this study, a natural polysaccharide (Sesamum radiatum gum) (SG) was extracted, characterized and used to formulate sustained release theophylline compacts to study the effect of varying alcohol concentrations (v/v) in dissolution media on drug release from these compacts. X-ray powder diffraction showed that the extracted gum was amorphous in nature with the powder having excellent compaction properties as observed with its compact being significantly harder than those prepared with pure hydroxypropyl methyl cellulose (HPMC) K4M. X-ray microtomography showed that the compacts produced were homogenous in nature, however, swelling studies showed failure of the compacts at the highest concentration of absolute ethanol used (40% v/v). Dissolution studies showed similarity at all levels of alcohol tested (f2 = 57–91) in simulated gastric (0.1 N HCl, pH 1.2) and intestinal fluids (phosphate buffer, pH 6.8) for the HPMC compacts whereas dissimilarity only occurred for the SG compacts at the highest alcohol concentration in both media (f2 = 35). The suitability of SG as a matrix former that can resist alcoholic effects therefore makes it suitable as an alternative polymer with wider applications for drug delivery.

Nitrogen-doped carbon nanotubes decorated poly (L-Cysteine) as a novel, ultrasensitive electrochemical sensor for simultaneous determination of theophylline and caffeine

In present study, a novel and facile electrochemical sensor based on glassy carbon electrode (GCE) modified with nitrogen-doped carbon nanotubes (N-CNT) decorated with poly (L-Cysteine) (PLCY) were fabricated and applied for the simultaneous voltammetric determination of theophylline (THEO) and caffeine (CAF). The morphology and structure of multilayer film modified on the surface of glassy carbon electrode were investigated successfully by Scanning Electron Microscope (SEM), Transmission Electron Microscope (TEM) and Raman Spectroscopy. And the properties of the modified electrode were investigated by Chronocoulometry (CC), Cyclic Voltammetry (CV) and Differential Pulse Voltammetry (DPV) were utilized to investigate the electrochemical behavior of THEO and CAF on the composite film modified electrode. The results showed that the determination towards THEO and CAF can be operated at the same potential window with the oxidation current peak separated and non-interfering respectively. Compared to the bare GCE, the PLCY/N-CNT/GCE can signally meliorate the electrocatalytic activity towards the oxidation of THEO and CAF with a remarkably increase in the anodic peak currents of 495.94% and 465.48%. Under the optimal conditions, the fabrication multilayer film sensor had excellent performances in determination towards THEO and CAF with a wide linear dynamic range from 0.10 to 70.0μM and 0.40–140.0μM, low detection limit (S/N = 3) of 0.033μM and 0.20μM, respectively. The PLCY/N-CNT/GCE sensor also had advantages as easy-made, high-sensitivity, stability and reproducibility. Moreover, it was successfully used to analyze the THEO and CAF in green tee, oral theophylline sustained release tablets and energy drink sample with a satisfactory result.

サーカディアンリズムから見た気管支喘息へのクロノセラピーの応用 : 第2報:気管支喘息患者のピークフローを用いた日内変動調査と各変動パターン別に対する徐放性テオフィリン製剤の効果

サーカディアンリズムから見た気管支喘息へのクロノセラピーの応用 : 第2報:気管支喘息患者のピークフローを用いた日内変動調査と各変動パターン別に対する徐放性テオフィリン製剤の効果

Prediction of Optimum Combination of Eudragit RS/Eudragit RL/Ethyl Cellulose Polymeric Free Films Based on Experimental Design for Using as a Coating System for Sustained Release Theophylline Pellets.

The physicochemical properties of free films made from different mixtures of sustained release polymers were investigated, and an optimum formulation coating on drug containing pellets, based on the study of free film was evaluated. In order to determine the effect of different variables on the permeability and swelling of films and procedure optimization, the experimental design was fulfilled based on the statistical method of a 3(3) full factorial design, and according to this method 27 formulations were prepared. The films were prepared using casting-solvent evaporation method. Water vapor permeability, the swelling and permeability of free films in both acidic and buffer media, were carried out. Then, the pellets containing theophylline were coated with the optimum formulation. The results of this study demonstrated that an increase in the free film thickness and Eurdragit RS ratio in films lowered the water vapor transmission (WVT), the swelling and the permeability of all formulations, while an increase in the quantity of ethylcellulose, up to a specific ratio (approximately 40%), decreased the permeability and swelling. The most optimum free film formulation was made up of 60% Eudragit RS and 40% ethylcellulose. Pellets coated with a 10% coating level of ethylcellulose and Eudragit RS (4:6) showed suitable release properties and could serve as a favorable sustained release system for theophylline.

Examining Small Intestinal Transit Time as a Function of Age: Is There Evidence to Support Age-Dependent Differences among Children?

The small intestine represents the region where the majority of drug and nutrient absorption transpires. Among adults, small intestinal transit kinetics is well delineated; however, the applicability of these values toward children remains unclear. This article serves to examine the relationship between age and mean small intestinal transit time (SITT) based on the available literature. In addition, the influence of alterations in intestinal transit time was explored among children using a model-based approach. Primary literature sources depicting SITT from children to adults were ascertained via the PubMed database. Data were limited to subjects without pathologies that could influence intestinal motility. Random-effect meta-regression models with between-study variability were employed to assess the influence of age on SITT. Three separate models with age as a linear or higher-order (i.e., second- and third-order polynomial) regressor were implemented to assess for the potential of both linear and curvilinear relationships. Examination of the influence of altered intestinal transit kinetics on the absorption of a sustained release theophylline preparation was explored among children between 8 and 14 years using physiologically based pharmacokinetic (PBPK) modeling. Age was not found to be a significant modulator of small intestinal transit within either the linear or higher-order polynomial meta-regression models. PBPK simulations indicated a lack of influence of variations in SITT on the absorption of theophylline from the examined sustained release formulation in older children. Based on the current literature, there is no evidence to suggest that mean SITT differs between children and adults.

Optimization on preparation conditions of calcium-crosslinked modified chitosan as potential matrix material for theophylline sustained-release beads and its evaluation of release kinetics

This study aimed to prepare theophylline loaded hydroxamated chitosan alpha-ketoglutaric acid (HKCTS) microspheres by ion crosslinking method, and optimize the process and formulation variables using response surface methodology. The independent variables studied were pH value, concentrations of Ca(Ⅱ) ion and HKCTS/theophylline ratio. The dependent variables (responses) were drug loading content and encapsulation efficiency. Mathematical equations and response surface plots were used to relate the independent and dependent variables. The release kinetics was evaluated by fitting the experimental data to standard release equations (zero-, first- and Higuchi equation). Results showed that the optimal conditions for microsphere formulation were 9.6 mg/mL Ca(Ⅱ)ion, 1:1 (g/g) HKCTS/theophylline ratio and pH 9.1, the drug loading content and encapsulation efficiency were 53.40% and 69.61%, respectively. The best fit was found with Higuchi model for the microspheres. The response surface methodology could provide a promising application for calcium cross-linked modified chitosan beads as a new matrix for controlled release of theophylline.

Japanese Guideline for Adult Asthma 2014.

Adult bronchial asthma (hereinafter, asthma) is characterized by chronic airway inflammation, reversible airway narrowing, and airway hyperresponsiveness. Long-standing asthma induces airway remodeling to cause intractable asthma. The number of patients with asthma has increased, and that of patients who die from asthma has decreased (1.5 per 100,000 patients in 2012). The aim of asthma treatment is to enable patients with asthma to lead a normal life without any symptoms. A good relationship between physicians and patients is indispensable for appropriate treatment. Long-term management with antiasthmatic agents and elimination of the causes and risk factors of asthma are fundamental to its treatment. Four steps in pharmacotherapy differentiate between mild and intensive treatments; each step includes an appropriate daily dose of an inhaled corticosteroid, varying from low to high. Long-acting β2-agonists, leukotriene receptor antagonists, and sustained-release theophylline are recommended as concomitant drugs, while anti-immunoglobulin E antibody therapy has been recently developed for the most severe and persistent asthma involving allergic reactions. Inhaled β2-agonists, aminophylline, corticosteroids, adrenaline, oxygen therapy, and others are used as needed in acute exacerbations by choosing treatment steps for asthma exacerbations depending on the severity of attacks. Allergic rhinitis, chronic obstructive pulmonary disease, aspirin-induced asthma, pregnancy, asthma in athletes, and cough-variant asthma are also important issues that need to be considered.

Invivo absorption behaviour of theophylline from starch-methyl methacrylate matrix tablets in beagle dogs

This study evaluates in vivo the drug absorption profiles from potato starch-methyl methacrylate matrices* using theophylline as a model drug. Healthy beagle dogs under fasting conditions were used for in vivo studies and plasma samples were analyzed by a fluorescence polarization immunoassay analysis (FPIA method). Non-compartmental and compartmental (population approach) analysis was performed to determine the pharmacokinetic parameters. The principle of superposition was applied to predict multiple dose plasma concentrations from experimental single dose data. An in vitro–in vivo correlation (IVIVC) was also assessed. The sustained absorption kinetics of theophylline from these formulations was demonstrated by comparison with two commercially available oral sustained-release theophylline products (Theo-Dur® and Theolair®). A one-compartment model with first order kinetics without lag-time best describes the absorption/disposition of theophylline from the formulations. Results revealed a theophylline absorption rate in the order FD-HSMMA≥Theo-Dur®≥OD-CSMMA>Theolair®≥FD-CSMMA. On the basis of simulated plasma theophylline levels, a twice daily dosage (every 12h) with the FD-CSMMA tablets should be recommended. A Level C IVIVC was found between the in vitrot50% and the in vivo AUC/D, although further optimization of the in vitro dissolution test would be needed to adequately correlate with in vivo data.