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1.
《Drug development and industrial pharmacy》2013,39(9):1036-1045
Background: Pharmaceutical cocrystallization is a promising alternative for improving the solubility and dissolution rate or manipulating other physical properties of active pharmaceutical ingredients. The objective of this investigation was to study the effect of cocrystallization with different cocrystal formers on physicochemical properties of mefloquine hydrochloride. Method: Cocrystals were prepared by solution crystallization method – mefloquine hydrochloride (414.8 mg, 1 mmol) and different cocrystal formers (1/2 mmol) were dissolved in 20 mL of ethanol with warming. Solution was cooled in ice bath for 6 hours. The crystals were isolated by filtration through a membrane (0.45 μm) and dried in the air. The pure drug and the prepared cocrystals were characterized in terms of saturation solubility, drug content, infrared spectroscopy, differential scanning calorimetry, powder X-ray diffraction, scanning electron microscopy, in vitro dissolution studies, and stability studies. Results: The cocrystals showed enhanced solubility and dissolution rate. The cocrystals were found to be stable over the period of 6 months confirmed from stability studies. Conclusion: Cocrystals resist the conversion of anhydrous form of drug into its hydrate which is responsible for the drugs less solubility and dissolution rate. 相似文献
2.
《Drug development and industrial pharmacy》2013,39(8):1197-1206
Objective: Venlafaxine is freely soluble In water and administered orally as hydrochloride salt In two to three divided doses. In the present investigation different release retarding matrices have been evaluated for sustained release of venlafaxine hydrochloride (VH) from the formulated tablets.Materials and methods: Sustained release matrix tablets were formulated using different hydrophilic, hydrophobic and waxy materials as matrix formers. Tableting was done by pre-compression, direct compression and hot melt granulation depending on the type of matrix material used and evaluated for different tests. The formulated tablets were compared with commercial venlafaxine products. In vitro drug dissolution profiles were fitted In different mathematical models to elucidate the release mechanism.Results: Dissolution data showed that commercial formulations Venlor XR® and Venfax PR® released the entire drug withIn 8?h where as the formulated tablets with hydroxypropylmethylcellulose (HPMC) and cetyl alcohol as matrix formers provided sustained release of drug for 14–15?h. The release was found to follow Hixson Crowel and Higuchi kinetics for HPMC and cetyl alcohol tablets, respectively.Conclusion: The developed matrix tablet formulations with HPMC and cetyl alcohol provided sustained release profiles for prolonged periods than commercial formulations. 相似文献
3.
Monika Nijhawan A. Santhosh P. R. Sathesh Babu C. V. S. Subrahmanyam 《Drug development and industrial pharmacy》2014,40(9):1163-1172
Context: Lornoxicam is an analgesic and anti-inflammatory drug of choice and belongs to Class II (low solubility) of BCS (Biopharmaceutical Classification System). Thus bioavailabilities problems are predominant.Objective: Through crystal engineering approach, a method was developed for obtaining multi-component cocrystals of lornoxicam using pharmaceutically acceptable compounds as guests.Materials and methods: Lornoxicam guest-free form was obtained from solution crystallization. Supramolecular synthon approach indicated that lornoxicam was in orthorhombic form. Further presence of intermolecular hydrogen bonding with layered structures was identified. Solvent drop grinding method permitted the formation of cocrystals of lornoxicam with catechol, resorcinol, benzoic acid, hydroxyquinone and 2,4 dihydroxy benzoic acid, all are capable of forming hydrogen bonding.Results and discussion: Lornoxicam cocrystals exhibited the difference in melting points and decomposition characteristics. The analysis of infrared (IR) indicated the shifting of characteristic bands of lornoxicam. The XPRD (X-Ray Powder Diffraction) pattern indicated the crystallinity of cocrystals and significant difference in 2θ value of intense peaks. Differential scanning calorimetry spectra of cocrystals denoted the changes in fusion endotherms, which are in agreements with melting points. The pH solubility profile of lornoxicam showed sigmoidal curve, which substantiated the pKa-dependent solubility. Lornoxicam cocrystals also exhibited a similar pH-solubility profile. Thus pairing of lornoxicam and coformers in the solution at high pH media was assumed. The in vitro dissolution studies of cocrystals were conducted at pH 4.0. The rapid rate of dissolution of cocrystals was observed in initial 10?min. The extent of dissolution was enhanced by 20% on account of cocrystallization.Conclusion: The lornoxicam cocrystals were obtained with improved physicochemical characteristics. 相似文献
4.
Shahram Emami Mohammadreza Siahi-Shadbad 《Drug development and industrial pharmacy》2018,44(6):1034-1047
Objectives: This study employed electrospray deposition (ESD) for simultaneous synthesis and particle engineering of cocrystals.Significance: Exploring new methods for the efficient production of cocrystals with desired particle properties is an essential demand.Methods: The possibility of cocrystal formation by ESD was examined for indomethacin-saccharin, indomethacin-nicotinamide, naproxen-nicotinamide, and naproxen-iso-nicotinamide cocrystals. Solutions of the drug and coformer at stoichiometric ratios were sprayed to a high electric field which caused rapid evaporation of the solvent and the formation of fine particles. The phase purity, size, and morphology of products were compared with reference cocrystals. Experiments were performed to evaluate the effects of stoichiometric ratio, concentration and solvent type on the cocrystal formation. Physical stability and dissolution properties of the electrosprayed cocrystals were also compared with reference cocrystals.Results: ESD was found to be an efficient and rapid method to produce cocrystals for all studied systems other than indomethacin-nicotinamide. Pure cocrystals only formed at a specific drug:coformer ratio. The solvent type has a weak effect on the cocrystal formation and morphology. Electrosprayed cocrystals exhibited nano to micrometer sizes with distinct morphologies with comparable physical stability with reference cocrystals. Nanococrystals of indomethacin-saccharin with a mean size of 219?nm displayed a threefold higher dissolution rate than solvent evaporated cocrystal.Conclusion: ESD successfully was utilized to produce pure cocrystals of poorly soluble drugs with different morphologies and sizes ranging from nano to micrometer sizes in one step. This study highlighted the usefulness of ESD for simultaneous preparation and particle engineering of pharmaceutical cocrystals. 相似文献
5.
《Drug development and industrial pharmacy》2013,39(6):971-988
AbstractThe preparatory step in the analysis of active drugs in tablet dosage forms has generally consisted of the grinding or milling of a given number of the tablets into a fine powder. Certain drugs formulated as tablets have been shown to undergo physical separation from other tablet components as a result of grinding. This phenomenon accounts, at least in part, for the poor reproducibility found in duplicate assays for these drugs in tablet composites. This same phenomenon also explains discrepancies between the average of the individual tablet assay values of samples prepared by direct dissolution, and the assay value of the corresponding composites.This paper illustrates this phenomenon using a problem dosage form and suggests methods of sample preparation that avoid segregation of ingredients. These methods include the direct dissolution of a representative number of individual tablets in a suitable solvent, the sieving and regrinding of the ground tablets, the grinding of a composite with a suitable organic solvent and the evaporation of the solvent, and the dissolution of the total composite tablet sample in a solvent. 相似文献
6.
AbstractThe use of soluble cocrystal for delivering drugs with low solubility, although a potentially effective approach, often suffers the problem of rapid disproportionation during dissolution, which negates the solubility advantages offered by the cocrystal. This necessitates their robust stabilization in order for successful use in a tablet dosage form. The cocrystal between carbamezepine and succinic acid (CBZ-SUC) exhibits a higher aqueous solubility than its dihydrate, which is the stable form of CBZ in water. Using this model system, we demonstrate an efficient and material-sparing tablet formulation screening approach enabled by intrinsic dissolution rate measurements. Three tablet formulations capable of stabilizing the cocrystal both under accelerated condition of 40?°C and 75% RH and during dissolution were developed using three different polymers, Soluplus® (F1), Kollidon VA/64 (F2) and Hydroxypropyl methyl cellulose acetate succinate (F3). When compared to a marketed product, Epitol® 200?mg tablets (F0), drug release after 60?min from formulations F1 (~82%), F2 (~95%) and F3 (~95%) was all higher than that from Epitol® (79%) in a modified simulated intestinal fluid. Studies in albino rabbits show correspondingly better bioavailability of F1–F3 than Epitol. 相似文献
7.
《Drug development and industrial pharmacy》2013,39(6):951-962
AbstractThe addition of a surfactanat into a tablet formulation appears to be attractive method of improve the drug release rate. The improved release rate is often associated with the effect of surfactant increasing the hydrophilicity of the dosage form thereby promoting drug dissolution. The findings of this investigation showed tha the presence of surfactant infulenced the tablet disintegration rate, producing a finer dispersion of disintergrated particles. It follows that the action of surfactant improving drug dissolution from tablets may be attributed ot the aciton of surfactnat producing fine disintegrated particles with correspondingly larger surface area for drug dissolution. It was also demonstrated that upon tablet disintergration the disinstegrated particles have a tri-moal frequency distribution. 相似文献
8.
Tarek A. Ahmed Mohammad A. A. Suhail Khaled M. Hosny Fathy I. Abd-Allah 《Drug development and industrial pharmacy》2018,44(1):66-81
Objective: Implementation of a new pharmaceutical technique to improve aqueous solubility and thus dissolution, enhancement of drug permeation, and finally formulation of a controlled release tablet loaded with glimepiride (GLMP).Significance: Improve GLMP bioavailability and pharmacokinetics in type II diabetic patients.Methods: Different polymers were used to enhance aqueous GLMP solubility of which a saturated polymeric drug solution was prepared and physically adsorbed onto silica. An experimental design was employed to optimize the formulation parameters affecting the preparation of GLMP matrix tablets. A compatibility study was conducted to study components interactions. Scanning electron microscope (SEM) was performed before and after the tablets were placed in the dissolution medium. An in vivo study in human volunteers was performed with the optimized GLMP tablets, which were compared to pure and marketed drug products.Results: Enhancement of GLMP aqueous solubility, using the polymeric drug solution technique, by more than 6–7 times when compared with the binary system. All the studied formulation factors significantly affected the studied variables. No significant interaction was detected among components. SEM illustrated the surface and inner tablet structure, and confirmed the drug release which was attributed to diffusion mechanism. The volunteer group administered the optimized GLMP tablet exhibited higher drug plasma concentration (147.4?ng/mL), longer time to reach maximum plasma concentration (4?h) and longer t1/2 (7.236?h) compared to other groups.Conclusions: Matrix tablet loaded with a physically modified drug form could represent a key solution for drugs with inconsistent dissolution and absorption profiles. 相似文献
9.
Priscileila Colerato Ferrari Dany Bruno Borella dos Santos Grossklauss Matheus Alvarez Fabiano Carlos Paixão Uilian Andreis Alexandre Giordano Crispim 《Drug development and industrial pharmacy》2014,40(8):1123-1131
Context: Alternating Current Biosusceptometry is a magnetically method used to characterize drug delivery systems. This work presents a system composed by an automated ACB sensor to acquire magnetic images of floating tablets.Objective: The purpose of this study was to use an automated Alternating Current Biosusceptometry (ACB) to characterize magnetic floating tablets for controlled drug delivery.Materials and methods: Floating tablets were prepared with hydroxypropyl methylcellulose (HPMC) as hydrophilic gel material, sodium bicarbonate as gas-generating agent and ferrite as magnetic marker. ACB was used to characterize the floating lag time and the tablet hydration rate, by quantification of the magnetic images to magnetic area. Besides the buoyancy, the floating tablets were evaluated for weight uniformity, hardness, swelling and in vitro drug release.Results: The optimized tablets were prepared with equal amounts of HPMC and ferrite, and began to float within 4?min, maintaining the flotation during more than 24?h. The data of all physical parameters lied within the pharmacopeial limits. Drug release at 24?h was about 40%.Conclusions: The ACB results showed that this study provided a new approach for in vitro investigation of controlled-release dosage forms. Moreover, using automated ACB will also be possible to test these parameters in humans allowing to establish an in vitro.in vivo correlation (IVIVC). 相似文献
10.
《Drug development and industrial pharmacy》2013,39(11):1802-1808
Context: Continuous processing is becoming popular in the pharmaceutical industry for its cost and quality advantages.Objective: This study evaluated the mechanical properties, uniformity of dosage units and drug release from the tablets prepared by continuous direct compression process.Materials and methods: The tablet formulations consisted of acetaminophen (3–30% (w/w)) pre-blended with 0.25% (w/w) colloidal silicon dioxide, microcrystalline cellulose (69–96% (w/w)) and magnesium stearate (1% (w/w)). The continuous tableting line consisted of three loss-in-weight feeders and a convective continuous mixer and a rotary tablet press. The process continued for 8?min and steady state was reached within 5?min. The effects of acetaminophen content, impeller rotation rate (39–254?rpm) and total feed rate (15 and 20?kg/h) on tablet properties were examined.Results and discussion: All the tablets complied with the friability requirements of European Pharmacopoeia and rapidly released acetaminophen. However, the relative standard deviation of acetaminophen content (10% (w/w)) increased with an increase in impeller rotation rate at a constant total feed rate (20?kg/h). A compression force of 12?kN tended to result in greater tablet hardness and subsequently a slower initial acetaminophen release from tablets when compared with those made with the compression force of about 8?kN.Conclusions: In conclusion, tablets could be successfully prepared by a continuous direct compression process and process conditions affected to some extent tablet properties. 相似文献
11.
《Drug development and industrial pharmacy》2013,39(6):949-964
AbstractA study was carried out to evaluate some parameters which may have an effect on the dissolution rate of prednisone from tablets. The parameters examined involving formulation were: diluent proportion (Lactose-starch), dissintegrant type (starch, explotab (sodium starch glycolate) type of binder (starch paste, gelatine water solution and PVP alcoholic solution), lubricant, and dye concentration. The Manufacturing variables studied were: method of manufacture (wet granulation, direct compression and double compression), granule size in wet granulation and tablet hardness. dissolution profiles of tablets storaged 2 months at 45°C were compared with those of fresh samples. Tablets prepared with prednisone five years old, tablets with fresh active ingredient and tablets with two different prednisone concentrations (5 and 50 mg per tablet) were used for other evaluations.In all cases micronized prednisone was used and all batches were physically and chemically evaluated before studying their dissolution following the USP basket method.The parameters studied that affected significatively dissolution rate of prednisone were: type of binder, lubricant concentration, method of manufacture, active ingredient, age and prednisone concentration. 相似文献
12.
Freeze drying: exploring potential in development of orodispersible tablets of sumatriptan succinate
Dalapathi Gugulothu Preshita Desai Pranav Pandharipande 《Drug development and industrial pharmacy》2015,41(3):398-405
The present investigation is aimed at development and characterization of sumatriptan succinate orodispersible tablets (ODTs) prepared by freeze drying technology. The tablet excipients were screened and the composition was optimized based on parameters which involved general appearance, tablet size and shape, uniformity of weight, mechanical properties, surface pH, moisture analysis, drug content, wetting time, in vitro and in vivo disintegration time. Furthermore, fourier transform infrared spectroscopy, differential scanning calorimetry, scanning electron micrograph of cross-section of the tablet and in vitro dissolution studies were performed. Studies revealed that formulation containing gelatin–mannitol (3.75% w/v and 3.5% w/v, respectively) with camphor as a volatile pore forming agent exhibited superior properties with disintegration time of less than 10?s. Furthermore, in vitro release studies revealed 90% release of drug from developed dosage form within 10?min, thus suggesting rapid drug dissolution followed by faster onset of action, which forms a strong rationale for development of ODTs of sumatriptan succinate. The developed technology is simple, which involves few steps and can be easily scaled up. Thus, it holds enormous potential for commercial exploitation. 相似文献
13.
Objective: The current investigation is focused on the formulation and in vivo evaluation of optimized solid self-nanoemulsifying drug delivery systems (S-SNEDDS) of amisulpride (AMS) for improving its oral dissolution and bioavailability.Methods: Liquid SNEDDS (L-SNEDDS) composed of Capryol? 90 (oil), Cremophor® RH40 (surfactant), and Transcutol® HP (co-surfactant) were transformed to solid systems via physical adsorption onto magnesium aluminometasilicate (Neusilin US2). Micromeretic studies and solid-state characterization of formulated S-SNEDDS were carried out, followed by tableting, tablet evaluation, and pharmacokinetic studies in rabbits.Results: Micromeretic properties and solid-state characterization proved satisfactory flow properties with AMS present in a completely amorphous state. Formulated self-nanoemulsifying tablets revealed significant improvement in AMS dissolution compared with either directly compressed or commercial AMS tablets. In vivo pharmacokinetic study in rabbits emphasized significant improvements in tmax, AUC(0–12), and AUC(0–∞) at p?<?.05 with 1.26-folds improvement in relative bioavailability from the optimized self-nanoemulsifying tablets compared with the commercial product.Conclusions: S-SNEDDS can be a very useful approach for providing patient acceptable dosage forms with improved oral dissolution and biovailability. 相似文献
14.
《Drug development and industrial pharmacy》2013,39(1-2):57-68
AbstractThe dissolution properties of controlled-release theophylline tablets containing acrylic resins are presented. Four different resins (Eudragit RSPM, RLPM, Sl00 and Ll00) were incorporated into theophylline tablets by direct compression techniques and the properties of the resulting dosage form were evaluated in dilute acid, buffer media pH 4.0 and simulated intestinal media pH 7.5. Tablets (500 mg) containing 300 mg of theophylline were prepared with each of the four resins and compressed to a hardness level of 6.5 to 7.5 kg. Excellent flow properties, weight uniformity and drug content uniformity were observed with all tablet formulations. Preliminary data suggest that three of the four resins tested showed great promise as a retardant in a matrix controlled drug delivery system. The dissolution properties of three commercially available sustained-release theophylline tablets were also determined. A comparison of profiles from TheodurR (300 mg) in acid and simulated intestinal media showed a similarity in release properties to those of theophylline in tablets containing the RLPM resin. 相似文献
15.
Yuki Fujisaki Tadashi Tsukune Motomu Funyû Mutsuo Okumura Tadashi Ukigaya Kenji Sugibayashi 《Drug development and industrial pharmacy》2013,39(2):207-217
ABSTRACTWe have developed a 200 mg and 400 mg sustained-release sodium valproate tablet that allows effective blood concentration of the active drug with once-a-day dosing. The controlled dissolution or sustained release of the drug was attained by a membrane-controlled system. A single-coating system did not adequately control the dissolution rate, and therefore double-coated tablets were prepared and a human pharmacokinetic study was conducted. With the 200 mg VPA-Na tablets, the nonfasting Cmax was only 20% higher than the fasting Cmax. An in vitro dissolution test was conducted to predict the effects of food on drug dissolution after administration of this tablet. A relatively good correlation was observed between the absorption profiles and the dissolution profiles of the drug. 相似文献
16.
《Drug development and industrial pharmacy》2013,39(12):1486-1496
Objective: The objective of this study was to investigate the effects of sodium lauryl sulfate (SLS) from different sources on solubilization/wetting, granulation process, and tablet dissolution of BILR 355 and the potential causes. Methods: The particle size distribution, morphology, and thermal behaviors of two pharmaceutical grades of SLS from Spectrum and Cognis were characterized. The surface tension and drug solubility in SLS solutions were measured. The BILR 355 tablets were prepared by a wet granulation process and the dissolution was evaluated. Results: The critical micelle concentration was lower for Spectrum SLS, which resulted in a higher BILR 355 solubility. During wet granulation, less water was required to reach the same end point using Spectrum than Cognis SLS. In general, BILR 355 tablets prepared with Spectrum SLS showed a higher dissolution than the tablets containing Cognis SLS. Micronization of SLS achieved the same improved tablet dissolution as micronized active pharmaceutical ingredient. Conclusions: The observed differences in wetting and solubilization were likely due to the different impurity levels in SLS from two sources. This study demonstrated that SLS from different sources could have significant impact on wet granulation process and dissolution. Therefore, it is critical to evaluate SLS properties from different suppliers, and then identify optimal formulation and process parameters to ensure robustness of drug product manufacture process and performance. 相似文献
17.
《Drug development and industrial pharmacy》2013,39(11):1720-1730
Objective: The purpose of this study was to develop hydroxypropylmethylcellulose (HPMC)-based sustained release (SR) tablets for tolterodine tartrate with a low drug release variation.Methods: The SR tablets were prepared by formulating a combination of different grades of HPMC as the gelling agents. The comparative dissolution study for the HPMC-based SR tablet as a test and Detrusitol® SR capsule as a reference was carried out, and the bioequivalence study of the two products was also conducted in human volunteers.Results: The amount of HPMC, the grade of HPMC and the combination ratio of different grades of HPMC had remarkable effects on drug release from the SR tablets. Both the test and reference products had no significant difference in terms of comparative dissolution patterns in four different media (f2 > 50). Furthermore, the dissolution method and rotation speed showed no effects on the drug release from the two products. The 90% confidence intervals of the AUC0–36 and Cmax ratios for the test and reference products were within the acceptable bioequivalence intervals of log0.8–log1.25.Conclusions: A HPMC-based SR tablet for tolterodine tartrate with a low release variation was successfully developed, which was bioequivalent to Detrusitol® SR capsule. 相似文献
18.
《Drug development and industrial pharmacy》2013,39(8):923-929
Context: The solid state purity of cocrystals critically affects their performance. Thus, it is important to accurately quantify the purity of cocrystals in the final crystallization product.Objective: The aim of this study was to develop a powder X-ray diffraction (PXRD) quantification method for investigating the purity of cocrystals. The method developed was employed to study the formation of indomethacin-saccharin (IND-SAC) cocrystals by mechanochemical methods.Materials and methods: Pure IND-SAC cocrystals were geometrically mixed with 1:1 w/w mixture of indomethacin/saccharin in various proportions. An accurately measured amount (550?mg) of the mixture was used for the PXRD measurements. The most intense, non-overlapping, characteristic diffraction peak of IND-SAC was used to construct the calibration curve in the range 0–100% (w/w). This calibration model was validated and used to monitor the formation of IND-SAC cocrystals by liquid-assisted grinding (LAG).Results: The IND-SAC cocrystal calibration curve showed excellent linearity (R2?=?0.9996) over the entire concentration range, displaying limit of detection (LOD) and limit of quantification (LOQ) values of 1.23% (w/w) and 3.74% (w/w), respectively. Validation results showed excellent correlations between actual and predicted concentrations of IND-SAC cocrystals (R2?=?0.9981).Discussion: The accuracy and reliability of the PXRD quantification method depend on the methods of sample preparation and handling. The crystallinity of the IND-SAC cocrystals was higher when larger amounts of methanol were used in the LAG method.Conclusion: The PXRD quantification method is suitable and reliable for verifying the purity of cocrystals in the final crystallization product. 相似文献
19.
《Drug development and industrial pharmacy》2013,39(8):1167-1174
Context: Mini-tablets are compact dosage forms, typically 2–3 mm in diameter, which have potential advantages for paediatric drug delivery. Extended release (ER) oral dosage forms are intended to release drugs continuously at rates that are sufficiently controlled to provide periods of prolonged therapeutic action following each administration, and polymers such as hypromelllose (HPMC) are commonly used to produce ER hydrophilic matrices.Objective: To develop ER mini-tablets of different sizes for paediatric delivery and to study the effects of HPMC concentration, tablet diameter and drug solubility on release rate.Methods: The solubility of Hydrocortisone and theophylline was determined. Mini-tablets (2 and 3 mm) and tablets (4 and 7 mm) comprising theophylline or hydrocortisone and HPMC (METHOCEL? K15M) at different concentrations (30, 40, 50 and 60%w/w) were formulated. The effect of tablet size, HPMC concentration and drug solubility on release rate and tensile strength was studied.Results and Discussion: Increasing the HPMC content and tablet diameter resulted in a significant decrease in drug release rate from ER mini-tablets. In addition, tablets and mini-tablets containing theophylline produced faster drug dissolution than those containing hydrocortisone, illustrating the influence of drug solubility on release from ER matrices. The results indicate that different drug release profiles and doses can be obtained by varying the polymer content and mini-tablet diameter, thus allowing dose flexibility to suit paediatric requirements.Conclusion: This work has demonstrated the feasibility of producing ER mini-tablets to sustain drug release rate, thus allowing dose flexibility for paediatric patients. Drug release rate may be tailored by altering the mini-tablet size or the level of HPMC, without compromising tablet strength. 相似文献
20.
Patrick M. Woster 《Drug development and industrial pharmacy》2013,39(3):399-400
AbstractThe preparation of a new scored 250 mg theophylline tablet is described, for which effects of particle size of the active principle, aspects of granulation and changes in tabletting settings were investigated.In vitro studies showed the dissolution rate from tablets prepared from theophylline of commercial quality (50 μm) or of selected particle size (30 μm) to be faster than that from tablets prepared from micronized theophylline (10 μm). In vivo studies in dog showed that only the tablet from theophylline of selected particle size has the same bioavailability as an aqueous solution.The scale up study showed that the characteristics of the tablets, including dissolution rate, are independent of the formulation factors. 相似文献