Theophylline Tablets Research Articles

Influence of design parameters on sustained drug release properties of 3D-printed theophylline tablets

The application of three-dimensional printing (3DP) in the pharmaceutical industry brings a broad spectrum of benefits to patients by addressing individual needs and improve treatment success. This study investigates the sustained release properties of 3DP tablets containing Theophylline (TPH), which is commonly used to treat respiratory diseases and recently having a comeback due to its potential in the treatment of conditions like Covid-19. Since TPH is a narrow therapeutic window (NTW) drug with serious side effects in the event of overdose, the release properties must be observed particularly closely. We employed a state-of-the-art single screw extrusion 3D printer, which is fed with granules containing the drug. By employing a Taguchi orthogonal array design of experiments (DOE), tablet design parameters and factor related process stability were sought to be evaluated fundamentally. Following this, examinations regarding tailored TPH dosages were undertaken and a relationship between the real printed dose of selected tablet designs and their sustained drug release was established. The release profiles were analyzed using different mathematical model fits and compared in terms of mean dissolution times (MDT). Finally, in-vivo/in-vitro correlation (IVIVC) and physiologically based pharmacokinetic (PBPK) modeling showed that a paradigm patient group could be covered with the dosage forms produced.

Oral Ergotamine versus Theophylline as Treatment of Post-dural Puncture Headache (PDPH) in Cesarean Section: A Randomized Clinical Trial

Introduction: Post Dural Puncture Headache is (PDPH) a relatively common complication of spinal anesthesia. This study aimed to compare the effect of oral administration of ergotamine and theophylline on PDPH in patients undergoing a cesarean section. Materials and Methods: This clinical trial was performed on 60 parturients undergoing cesarean section with PDPH. A tablet of theophylline (100 mg) or methyl ergotamine C (1 mg plus 100 mg caffeine) every 8 hours for 24 hours was administered randomly to patients referred to the hospital with PDPH. Using a checklist, demographic information, history of previous PDPH, number of punctures and intensity, location, and onset time of headache were collected. Intensity and duration of PDPH in the first 24 hours after surgery were the primary outcomes and nausea, vomiting, and vertigo were considered secondary outcomes. The intensity of the headache was assessed using Visual Analog Scale (VAS) before and within the first 24 hours after drug administration. Results and Discussion: In both groups, the VAS of headache significantly decreased at 2, 8, and 24 hours after administration of theophylline and ergotamine compared to pre-intervention time (theophylline from 8.6 ± 1.1 to 0.2 ± 0.1 and ergotamine from 8.6 ± 1.5 to 0.4 ± 0.2). However, the intensity of headaches was not different between the two groups at 2, 8, and 24 hours after the intervention. Duration of headache was similar in both groups (15.7 ± 5.9 in the theophylline group versus 17.5 ± 14.2 ergotamine group). In terms of secondary outcomes of nausea, vomiting, and vertigo, both groups were comparable. Conclusion: Oral administration of theophylline and ergotamine are similarly effective in reducing PDPH in cesarean sections. Clinical Trial Registration Number: IRCT20120915010841N14.

Effect of pH, Ionic Strength and Agitation Rate on Dissolution Behaviour of 3D-Printed Tablets, Tablets Prepared from Ground Hot-Melt Extruded Filaments and Physical Mixtures

With the current focus on 3D-printing technologies, it is essential to understand the processes involved in such printing methods and approaches to minimize the variability in dissolution behaviour to achieve better quality control outcomes. For this purpose, two formulations of theophylline tablets were prepared using hydroxypropyl cellulose (HPC) and ethyl cellulose (EC). Among the two types of tablets, three different methods (physical mixture (PM), hot-melt extrusion (HME) and 3D-printing fused deposition modelling (FDM)) were applied and their dissolution behaviours were studied under various conditions using a biodissolution tester. This was carried out at pH values of 1.2, 2.2, 5.8, 6.8, 7.2 and 7.5, mimicking the medium in the gastrointestinal tract. Dissolution tests under two dipping rates (10 dpm and 20 dpm) and two ionic strengths (0.2 M and 0.4 M) were conducted to mimic fed and fasting conditions. The dissolution efficiency (DE%), release rate, similarity factor (f2) and difference factor (f1) were calculated. When comparing the DE%, the formulation containing EC showed less sensitivity to changes in the dipping rate and ionic strength compared to the HPC formulation. As for the manufacturing method, 3D-printing FDM could improve the robustness of the dissolution behaviour of both formulations to dipping rate changes. However, for ionic strength changes, the effect of the manufacturing method was dependent on the formulation composition. For example, the 3D-printed tablets of the HPC formulation were more sensitive to changes in ionic strength compared to the EC-containing formulation. The release mechanism also changed after the thermal process, where n values in the Korsmeyer-Peppas model were much higher in the printing and HME methods compared to the PM. Based on the formulation composition, the 3D-printing method could be a good candidate method for tablets with a robust dissolution behaviour in the GI tract. Compared to HPC polymers, using hydrophobic EC polymers in printable formulations can result in a more robust dissolution behaviour in fed and fasting states.

UJI FISIK FORMULASI TABLET FLOATING TEOFILIN DENGAN MATRIK HPMC

The purpose of this study was to determine the physical properties of theophylline floating tablet formulation with HPMC as matrix. Floating tablets of theophylline is manufactured by direct compression. Composition per tablet formulation consisting of theophylline 270 mg, HPMC, avicel, magnesium stearate, and sodium bicarbonate. The results of data showed average of tablet weight uniformity 501mg, tablet hardness 6,99 kg, tablet friability 0,593%, disintegration time of tablets 738 seconds, floating lag time (FLT) 584,3 seconds and floating duration time (FDT) more than 8 hours. Floating tablet formulation of theophylline resulted in a good physical test.

Formulation and Evaluation of Controlled Release Theophylline Tablets using Grewia spp Gum as Binder

The major reason for development of new drug delivery system is based largely on promoting therapeutic outcome and minimizing toxic effect of a drug by increasing the amount and persistence of a drug in target cells areas, while reducing exposure of the drug to non-target cells. In this study, Grewia spp gum obtained from Grewia spp pods was extracted and used as binder and release retardant in the formulation of controlled release theophylline tablets. A total of six (6) batches of the tablets were produced with carried concentrations of the test gum by wet granulation technique. To produce the tablets, various granules were formulated via wet granulation and characterized by measuring flow and packing properties. Granules with adequate flow properties were compressed to tablets. Tablets so formed were evaluated for hardness, percentage friability, weight variability and drug release profiles. The percentage yield was 18.64% and the pH of the test gum was 6.15. The angle of repose, bulk density, tapped density and Carr’s index of the formulated granules ranged from 22.48±0.00 to 24.90±0.00˚, 0.53±0.03 to 0.67±0.00g/ml, 0.67±0.02 to 0.82±0.00g/ml and 18.29±0.00 to 22.06±0.26% respectively. Resultant tablets hardness values of 3.69±0.45 to 13.39±0.65kgF and friability percentage of 0.40± 0.00 to 2.56%±0.01% were also obtained. The formulated theophylline granules showed good flow properties and compressibility. Thus, the study revealed that the test gum has comparable binding effect to Eudragit RS 100 at a ratio of 2:1. We recommend further studies to rule out any interaction of Grewia spp gum with theophylline in controlled release theophylline tablets.

An Insight into the Impact of Thermal Process on Dissolution Profile and Physical Characteristics of Theophylline Tablets Made through 3D Printing Compared to Conventional Methods.

The dissolution profile is of great importance in drug delivery and is affected by the manufacturing method. Thus, it is important to study the influence of the thermal process on drug release in emerging technologies such as 3D printing-fused deposition modeling (FDM). For this purpose, the characteristics of 3D printed tablets were compared to those of tablets prepared by other thermal methods such as hot-melt extrusion (HME) and non-thermal methods such as physical mixture (PM). Theophylline was used as a drug model and blends of ethyl cellulose (EC) and hydroxypropyl cellulose (HPC) were used as a matrix former. The solid state of the drug in all formulations was investigated by differential scanning calorimetry, X-ray powder diffraction, and Fourier-transformed infrared spectroscopy. All studied tablets had the same weight and surface area/volume (SA/V). Dissolution data showed that, for some formulations, printed tablets interestingly had a faster release profile despite having the highest hardness values (>550 N) compared to HME and PM tablets. Porosity investigations showed that 100% infill printed tablets had the highest porosity (~20%) compared to HME (<10%) and PM tablets (≤11%). True density records were the lowest in printed tablets (~1.22 g/m3) compared to tablets made from both HME and PM methods (~1.26 g/m3), reflecting the possible increase in polymer specific volume while printing. This increase in the volume of polymer network may accelerate water and drug diffusion from/within the matrix. Thus, it is a misconception that the 3D printing process will always retard drug release based on increased tablet hardness. Hardness, porosity, density, solid-state of the drug, SA/V, weight, and formulation components are all factors contributing to the release profile where the total balance can either slow down or accelerate the release profile.

Effects of crosslinking on the physical solid-state and dissolution properties of 3D-printed theophylline tablets

Crosslinking is an established treatment to alter the physicochemical and functional properties of polymers through the creation of bonds between the polymer chains. Polymers can be crosslinked via radiation in the presence of photo-initiator. The aim of the present study was to formulate 3D-printed theophylline (THEO) tablets using polyethylene oxide (PEO) as a carrier polymer, and to study the influence of crosslinking on the drug release behavior. The tablets were 3D-printed using the aqueous solution of PEO and THEO (80:20 w/w) with a micro-extrusion-based printing setup. A photo-initiator (4-hydroxybenzophenone) was added into the printing solutions, and the injectability of the solutions was investigated prior to printing. The 3D-printed tablets were crosslinked after printing using ultraviolet (UV) or gamma-radiation, and crosslinking was verified by means of Fourier-transform infrared (FTIR) spectroscopy. The maximum injection force of aqueous printing solutions of PEO and THEO was close to that observed with the pure PEO solution. Increasing the number of printing layers in the 3D-printed tablets resulted in a slower drug release in vitro. Gamma-radiation in a nitrogen environment and UV-crosslinking made the carrier polymer (PEO) less water-soluble, but such crosslinking did not affect the release rate of the tablets. Surprisingly, even faster drug release behavior was found with the crosslinked 3D-printed tablets compared to that of non-crosslinked tablets. More research work is needed on the impact of 3D-printed tablet layering thickness and crosslinking for tailoring drug release behavior.

Swallowing Gel for Patients with Dysphagia: A Novel Application of Chitosan.

Dysphagia refers to difficulty swallowing certain foods, liquids, or pills. It is common among the elderly with chronic diseases who need to take drugs for long periods. Therefore, dysphagia might reduce compliance with oral drug administration in the aging population. Many pharmaceutical companies search for new products to serve as swallowing aids. Existing products are expensive and do not suit all geriatric patients. Therefore, this study aimed to develop and investigate pill swallowing aid gels prepared from carboxymethyl cellulose and chitosan. We formulated gels by dissolving different concentrations of carboxymethyl cellulose and low or high molecular weight chitosan in solvents to find appropriate gel rheology properties. We then added several portions of glycerin as the glidant of the formulation. We found that the optimized gel formulation was 6.25% (w/w) chitosan with a molecular weight of 80–120 kDa dissolved in 1.2% acetic acid and 4% (w/w) glycerin. The developed pill swallowing gel’s rheology was pseudoplastic with a viscosity of 73.74 ± 3.20 Pa⸱s. The developed chitosan gel had enhanced flow ability; it allowed the pill to cross a 300 mm tube within 6 s, while the reference product took 3 s. Even though the reference product could carry the pill in the tube faster, the chitosan gel better covered the pill, making it more convenient to use. Finally, using a theophylline tablet as a model tablet dosage form, we assessed the gel’s effect on drug disintegration and dissolution. The chitosan gel delayed the tablet disintegration time by about 3–7 min and slightly affected the theophylline dissolution rate. Lastly, all gels were physically stable after a month of storage in the stress condition. These results show the feasibility of manufacturing a chitosan gel usable as a pill swallowing gel for patients with dysphagia.

UJI FISIK FORMULASI TABLET FLOATING TEOFILIN DENGAN MATRIK HPMC

The purpose of this study was to determine the physical properties of theophylline floating tablet formulation with HPMC as matrix. Floating tablets of theophylline is manufactured by direct compression. Composition per tablet formulation consisting of theophylline 270 mg, HPMC, avicel, magnesium stearate, and sodium bicarbonate. The results of data showed average of tablet weight uniformity 501mg, tablet hardness 6,99 kg, tablet friability 0,593%, disintegration time of tablets 738 seconds, floating lag time (FLT) 584,3 seconds and floating duration time (FDT) more than 8 hours. Floating tablet formulation of theophylline resulted in a good physical test.Keyword: floating, theophylline, HPMC, tablet

Evaluation Profile In Vitro Release Gastroretentive High Density Tablet Theophylline Using Sodium Alginate and PVP

The high-density gastroretentive dosage forms was made a high-density theophylline tablets 250 mg by wet granulation method in three formulas with combine the polymer concentration. The polymer used sodium alginate and PVP K30, where the 1st formula ratio of sodium alginate: PVP K30 (18.75%: 5%), the 2nd formula ratio of sodium alginate: PVP K30 (18.75%: 2, 5%) and 3th formula ratio of sodium alginate: PVP K30 (12.5%: 2.5%). The third formula were evaluated with weight uniformity test, size uniformity test, hardness test, drug content test, in vitro release test, as well as the determination of the kinetics of drug release. The result showed the uniformity weights of the formula ranges 250.12mg-250.70mg, the uniformity size of the formula ranges 0.81cm for diameter tablet and 0.42cm-0.44cm for thick tablet, the hardness test ranges from 90N-180N. Results obtained for drug content was 106.965% formula 1st, formula 2nd is 127.625% and for formula 3th is 115.976%. Release kinetic profiles show formula 1st and 2nd used Higuchi equation and formula 3th used the first-order equation. By these three formula, 1st formula was considered the best views of drug content and release kinetics.

A Controlled Release Theophylline Delivery System Based on a Bilayer Floating System.

Bilayer floating drug delivery is an approach that helps to overcome the shortcomings of single-layered tablets. There is little or no fluctuation of the drug in the blood stream or tissue, while control is enabled over the time and site of drug release. In the current study, bilayer theophylline matrix tablets were formulated by double compression and evaluated using granules produced by polymeric granulation and simple coacervation techniques. Bilayer floating theophylline tablets containing an immediate release layer (IRL) and a sustained release layer (SRL) were prepared. Granules for the IRL section were produced by wet granulation, while those for the SRL section were produced by polymeric granulation and simple coacervation techniques using Eudragit RL100 and carboxymethyl cellulose (CMC) as binder. The resulting granules were characterized for flowability and packing properties. Granules with adequate flow were compressed into flat-faced tablets 12 mm in diameter using a single punch tableting machine at an arbitrary load of 28 kgF on a load scale. The tablets were evaluated for hardness, weight variability, disintegration, friability, swelling index, floating time, and in vitro drug release. The angle of repose and Hausner ratio were 29.07±0.330 to 40.08±0.660 and 1.07±0.01 to 1.28±0.01, respectively. Tablets hardness values ranged from 4.74±0.36 to 9.84±0.49 kgF, while percentage friability ranged from 0.5% to 1.51%. Floating lag time was between 1±0.41 and 9±0.71 min, while the total floating time was between 1 min and 9 h. Over 50% of the drug was released within 7 h. Drug release from the tablets showed a prompt release phase and an extended release phase. Therefore, appropriate combination of Eudragit and CMC and the right reagent can produce well retarded bilayer floating tablets.

3D printing of extended-release tablets of theophylline using hydroxypropyl methylcellulose (HPMC) hydrogels.

An extrusion based 3D printer was used to prepare the semi-solid tablets with different drug loading dosages (75, 100, 125mg) under ambient temperature. The active pharmaceutical ingredient, theophylline, was uploaded within the hydrogels prepared of hydroxypropyl methylcellulose (HPMC) K4M or E4M. The HPMC concentrations were adjusted to different levels (10 and 12% w/w) to fulfill the requirements for 3D printing. Rheological and textural properties, as well as release profiles, were significantly affected by the type and concentration of excipient regardless of theophylline doses used. The printing material should exhibit shear-thinning behavior, keeping yield stress less than 4000Pa and a loss factor (tanδ=G''/G') between 0.2 and 0.7, especially for 3D printing purposes using the current platform. The SEM images demonstrated that the hydrogel matrix exhibited a porous structure, which had the potential to encapsulate the theophylline clusters within its microstructure. The in vitro dissolution test showed that the release of all tablets was extended over 12h, and the calculation of drug release kinetic models revealed that the 3D printed HPMC matrices release the theophylline by diffusion and erosion mechanisms. The excipient HPMC K4M 12% w/w hydrogel was optimal to load the theophylline with flexible dosage combinations due to the great extrudability and shape retention ability. The exploration of rheological properties was investigated in this study, and the results revealed that it is a feasible method to predict the SSE 3D printability and quality of hydrogel-API blend materials for the drug delivery system.

An innovative wax-based enteric coating for pharmaceutical and nutraceutical oral products.

In this work, a novel enteric coating based on natural waxes and alginate was reported. Initially, theophylline tablets were coated with emulsified ceresin wax in heated aqueous alginate solution using a fluidised bed coating technology. A coating level of 10% proved sufficient to prevent tablets from uptaking gastric medium (<5%) and produced a delayed release profile that complies to the pharmacopeial criteria of enteric coating release. Then, a wide range of emulsions based on other natural waxes (white beeswax, yellow beeswax, cetyl palmitate, carnauba wax or rice bran wax) yielded coatings with similar disintegration times and release profiles. Interestingly, the ceresin-based coating showed a superior performance at inhibiting acid uptake and enabling highly pH-responsive drug release in comparison to different commercially available GRAS enteric coating products (Eudraguard® Control, Swanlac® ASL10, and Aquateric™ N100). The coating was stable for 6months at 30°C and 65% RH. This innovative approach of applying hot O/W emulsion of natural waxes yielded an aesthetically attractive and stable coating with gastric protection and pH-sensitive release properties. The novel coating can be an efficient and promising alternative to overcome the shortcomings of current GRAS grade enteric coating products.

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.

A novel natural GRAS-grade enteric coating for pharmaceutical and nutraceutical products

In this study, enteric coatings based exclusively on naturally occurring ingredients were reported. Alginate (Alg) and pectin (Pec) blends with or without naturally occurring glyceride, glycerol monostearate (GMS), were initially used to produce solvent-casted films. Incorporating GMS in the natural polymeric films significantly enhanced the acid-resistance properties in gastric medium. Theophylline tablets coated with Alg-Pec blends without GMS disintegrated shortly after incubation in gastric medium (pH 1.2), leading to a premature and complete release of theophylline. Interestingly, tablets coated with Alg-Pec blends that contain the natural glyceride (GMS) resisted the gastric environment for 2h with minimal drug release (<5%) and disintegrated rapidly following introduction to the intestinal medium, allowing a fast and complete drug release. Furthermore, the coating system proved to be stable for six months under accelerated conditions. These findings are particularly appealing to nutraceutical industry as they provide the foundation to produce naturally-occurring GRAS based enteric coatings.

Formulation and &lt;i&gt;In Vitro &lt;/i&gt;Evaluation of Gastroretentive Theophylline Floating Tablets

The main aim of the present investigation was to formulate and evaluate gastroretentive floating tablets of theophylline. Theophylline, a brochodialator, used in the treatment of asthma, has good absorption at the gastric pH. Therefore, a floating drug delivery system in a gastric pH could deliver the drug in a slow and sustained manner which could be a useful for broncho dilation in the treatment of asthma. The formulated gastroretentive tablets of theophylline were evaluated for various parameters such as weight variation, hardnesss, friability, drug content, swelling index, buoyancy time and drug release studies. Among the different formulations, formulation F7 prepared using HPMC:Carbopol (1:1 ratio) exhibited better release profile (93.36%) for 8 hours and this batch was selected as an ideal batch. The release of theophylline from the ideal batch was found to follow diffusion mechanism.

Fabrication of Intragastric Floating, Controlled Release 3D Printed Theophylline Tablets Using Hot-Melt Extrusion and Fused Deposition Modeling.

This work presents a novel approach for producing gastro-retentive floating tablets (GRFT) by coupling hot-melt extrusion (HME) and fused deposition three-dimensional printing (3DP). Filaments containing theophylline (THEO) within a hydroxypropyl cellulose (HPC) matrix were prepared using HME. 3DP tablets with different infill percentages and shell thickness were developed and evaluated to determine their drug content, floating behavior, dissolution, and physicochemical properties. The dissolution studies revealed a relationship between the infill percentage/shell thickness and the drug release behavior of the 3DP tablets. All the developed GRFTs possessed the ability to float for 10 h and exhibited zero-order release kinetics. The drug release could be described by the Peppas–Sahlin model, as a combination of Fickian diffusion and swelling mechanism. Drug crystallinity was found unaltered throughout the process. 3DP coupled with HME, could be an effective blueprint to produce controlled-release GRFTs, providing the advantage of simplicity and versatility compared to the conventional methods.

Novel Gastroretentive Floating Pulsatile Drug Delivery System Produced via Hot-Melt Extrusion and Fused Deposition Modeling 3D Printing.

This study was performed to develop novel core-shell gastroretentive floating pulsatile drug delivery systems using a hot-melt extrusion-paired fused deposition modeling (FDM) 3D printing and direct compression method. Hydroxypropyl cellulose (HPC) and ethyl cellulose (EC)-based filaments were fabricated using hot-melt extrusion technology and were utilized as feedstock material for printing shells in FDM 3D printing. The directly compressed theophylline tablet was used as the core. The tablet shell to form pulsatile floating dosage forms with different geometries (shell thickness: 0.8, 1.2, 1.6, and 2.0 mm; wall thickness: 0, 0.8, and 1.6 mm; and % infill density: 50, 75, and 100) were designed, printed, and evaluated. All core-shell tablets floated without any lag time and exhibited good floating behavior throughout the dissolution study. The lag time for the pulsatile release of the drug was 30 min to 6 h. The proportion of ethyl cellulose in the filament composition had a significant (p < 0.05) effect on the lag time. The formulation (2 mm shell thickness, 1.6 mm wall thickness, 100% infill density, 0.5% EC) with the desired lag time of 6 h was selected as an optimized formulation. Thus, FDM 3D printing is a potential technique for the development of complex customized drug delivery systems for personalized pharmacotherapy.

Formulation of Extended Release Theophylline Tablets Experimental, Modelling and Bioequivalence Studies

Extended release drugs formulations are intended to continuously release medication over a prolonged period, after a single dose. Drugs which have a narrow therapeutic window and a moderate half life are good candidates for such formulations. One approach to such formulations is to embed the drug in a matrix which 'would act as a release retardant. We describe here our studies on the formulations of an extended release theophylline tablet using polymer matrices. Different acrylate copolymers sold in the market under the "Eudragit" label were subjected to experiment. Microcrystalline cellulose and calcium sulphate dihydrate were used as filler excepients. The theophylline release patterns of the different formulations were studied, at 37aC in phosplate buffers. The theophylline concentration were measured by Ul/ absorption spectroscopy A careful study of the release patterns of different formulations let to a formulation using Eudragit=E RSPO, a trimenthylammonioethyl methacrylate copolymer and calcium sulphate dihydrate, which conformed with the following release pattern in accordance with USP 25. Time (hours) % Drug Released 1 10 - 30 2 30 - 55 4 55 - 80 8 &gt;80 This formulations 'was used to prepare tablets with two dosages, paediatric dose (125 mg) and adult dose (250 mg). The adult dose was subjected to a bioequivalence study against an established commercially available slow release 250 mg formulation (Neulin 250 SR, 3M Pharmaceuticals, Australia) Twenty healthy male volunteers participated in the study. Theophylline concentrations in serum were determined by Fluorescence Polarization Immunoassay. There was no significant difference between the two formulations in basic bio availability and pharmacokinetic parameters (AUC CiliaIa'nd Tlllal The new Theophylline ER 125 mgformulation developed is nOH'being manufactured by the State Pharmaceutical Manufacturing Corporation (SPMC). a. State Pharmaceutical Manufacturing Corporation, Sri Johne Kothalawala Estate, Ratmalana, Sri Lanka 071-1815117 b. Dean Faculty 0.( Natural Science, University of Sri Jayawrdanapura, Nugegoda c. Pharmacology Division, Faculty of Medicine, University of Sri Jayawrdanapura, Nugegoda.

Optimasi Konsentrasi Amylum Sagu (Metroxylon rumphii) sebagai Co-Processed pada Pembuatan Tablet Teofilin

Tablet preparations are widely used many people for treatment, so the level of production of tablet preparations is quite large and always develops in its formulation. Excipients are generally used in the form of 95% imported materials which are relatively expensive so that production costs will affect the price of tablet preparations which will be more expensive. Based on these considerations, this study uses Indonesian natural excipient with a relatively low cost in the form of sago amylum. This study combines sago amylum and Avicel pH 101 with 5 concentration variations, 90%: 10% (formula 1), 80%: 20% (formula 2), 70%: 30% (formula 3), 60%: 40% (formula 4), and 50%: 50% (formula 5) which produces a co-processed excipient. This co-processed was applied in the manufacture of the Theophylline tablet as a filler, binder and shredder with the direct compression method and tested based on parameters in the Indonesian Pharmacopoeia V. Data analysis using Design Expert® version 11 software to obtain the optimum formula. The co-processed characterization produced has optimum flow properties which are 11.11 g / sec, compressibility = 3.0%, and the stationary angle = 32.0 ° and evaluation of tablet quality uniformity CV = 10.3, hardness x̅ = 6 , 2 kg, fragility = 1.8%, and 46.2 seconds destroyed time. Based on the analysis by Simplex Lattice Design method, it is proved that the more amylum sago concentration increases friability and decreases hardness, while more of Avicel pH 101 decreases friability and increases hardness. It is concluded with the Design Expert software analysis, the optimum co-processed formula was obtained in the form of a combination of 50% sago amylum; 18,18% pasta amylum sago and 31.82% Avicel pH 101.