Dry Tablets Research Articles

Modeling moisture change of packaged dry tablet dosage forms under consumer use condition

A simple mathematical model based on product’s moisture sorption isotherm and package’s moisture transmission was developed to predict moisture content of dry solid tablets during consumers’ use, which is useful for determination of in-use shelf life (ISL) or secondary shelf life. The moisture increase depending on amount of product remaining in the package was accounted for in the mass balance equation on the package. The model was first verified by literature data of desiccant canisters in a plastic bottle of high density polyethylene exposed to two environmental conditions (25 °C and 60% relative humidity (RH); 40 °C and 75% RH) simulating in-use of removing one canister each day. Then an experimental work was conducted on dry refresher candies in a polyethylene terephthalate bottle at 25 °C with two tablets taken out every day, which confirmed the model’s capability to predict the product moisture content during in-use storage of 76% and 90% RH. Its use can provide science-based accurate determination of ISL, which may work as consumer guideline. The model is also expected to be helpful for recommending management scheme of whole product life.

A randomized, crossover study to evaluate α-tocopherol bioavailability via a microemulsion gel or dry tablet delivery in healthy adults.

Vitamin E (α-tocopherol) is an essential micronutrient for human health and optimal physiological function. Inadequacy may be common due to a lack of bioavailability. The use of dietary lipids alongside other emulsification agents may elicit more robust serum concentrations of α-tocopherol via improved bioavailability. Therefore, the aim of the study was to examine oral bioavailability of two delivery methods of α-tocopherol, (1) a microemulsion gel formula composed of dietary lipids and other emulsification agents and (2) a dry solid tablet over 12 hours. Twelve participants (age = 37.3 ± 9.6 years; height = 173.4 ± 11.8 cm; body mass = 71.2 ± 10.0 kg) participated in a double-blind, randomized, crossover trial comparing two delivery methods both dosed at 288 mg of α-tocopherol. Serum α-tocopherol concentrations were assessed from blood donated by participants at pre-consumption, 2-, 4-, 8-, and 12-hour post-consumption. Study conditions were separated by a 7-day washout. The microemulsion gel formula delivery demonstrated significantly greater area under the curve (p < 0.001) and serum concentration maximums (p = 0.003) for serum α-tocopherol compared to the tablet delivery. No significant differences were detected between conditions for the time to reach concentration maximums (p = 0.375). We conclude that a mixture of dietary lipids and emulsification agents in the form of a microemulsion gel formula was able to significantly improve bioavailability of serum α-tocopherol compared to a tablet by yielding higher serum α-tocopherol maximum concentrations and area under the curve over a 12-hour study period despite dosage being matched.

Radiation initiated synthesis of (carboxymethyl cellulose/polyacryalmide) hydrogels with polyprotic acid moieties and their utilization in nicotinic acid release

AbstractHydrogels of (carboxymethyl cellulose/polyacrylamide/polyprotic acids) were synthesized via gamma‐irradiation as green initiator. The polyprotic acids were used are oxalic, tartaric, citric and maleic. Effects of irradiation dose and polyprotic acids concentration on gelation (%) and swelling (%) are investigated. The swelling of hydrogels were conducted in the range of pH levels are from 1 to 12 at 37°C. The outcome hydrogels were characterized different techniques of Fourier transform infrared spectroscopy, thermal gravimetric analysis and derivative thermogravimetry, X‐ray diffraction, and scanning electron microscopy. The results confirmed the formation of respective hydrogels. Hydrogels were exploited in release of nicotinic acid as model of drug release. Dry tablets from hydrogels were fabricated as cylindrical discs. Dry hydrogels tablets were subjected to two different pH levels (i) simulated gastric fluid of pH level 1.2 and (ii) simulated intestinal fluid of pH level 7.5. The outcome results showed that there is a difference of nicotinic acid release quantity between the two pH levels. Further, different kinetic models of zero‐order, Korsmeyer–Peppas, Higuchi and Weibull were used to fit the experimental data. Through the results declared that the best fitting model was Weibull.

Visualising liquid transport through coated pharmaceutical tablets using Terahertz pulsed imaging

Dissolution of pharmaceutical tablets is a complex process, especially for coated tablets where layered structures form an additional barrier for liquid transport into the porous tablet matrix. A better understanding of the role of the coating structure in the mass transport processes that govern drug release, starting with the wetting of the coating layer by the dissolution medium, can benefit the formulation design and optimisation of the production. For this study, terahertz pulsed imaging was used to investigate how dissolution medium can penetrate coated tablets. In order to focus on the fundamental process, the model system for this proof-of-principle study consisted of tablet cores made from pure microcrystalline cellulose compacted to a defined porosity coated with Opadry II, a PVA-based immediate release coating blend. The coating was applied to a single side of flat-faced tablets using vacuum compression moulding. It was possible to resolve the hydration of the coating layer and the subsequent liquid ingress into the dry tablet core. The analysis revealed a discontinuity in density at the interface between coating and core, where coating polymer could enter the pore space at the immediate surface of the tablet cores during the coating process. This structure affected the liquid transport of the dissolution medium into the core. We found evidence for the formation of a gel layer upon hydration of the coating polymer. The porosity of the tablet core impacted the quality of coating and thus affected its dissolution performance (r = 0.6932 for the effective liquid penetration rate RPeff and the core porosity). This study established a methodology and can facilitate a more in-depth understanding of the role of coating on tablet dissolution.

Development of a mafedine lyophilizate for parenteral use

Introduction. Cerebrovascular disease (CVD) is the most important medical and social problem of modern neurology because they have the highest rates of morbidity, mortality and disablement in the population. The growing incidence of CVD as a result of an aging population worldwide requires the emergent development of therapeutics, diagnostic and preventive tools. However, the development of drugs for the treatment of brain diseases has limitations due to the presence of the blood-brain barrier, which protects the brain against most molecules from the bloodstream entering the central nervous system. At the St. Petersburg State Chemical Pharmaceutical University of the Ministry of Health of Russia the alpha-2 adrenergic agonist mafedine was synthesized, which has mild psychostimulant and anxiogenic effects and which may be used in the treatment of traumatic brain injury as a neuroprotective agent.Aim. The development of a dosage form of mafedine in order to improve its penetration into the central nervous system.Materials and methods. Mafedine (pharmaceutical substance) [6-oxo-1-phenyl-2-(phenylamino)-1,6-dihydropyrimidin-4-olate sodium] (St. Petersburg State Chemical-Pharmaceutical University of the Ministry of Health of Russia); lecithin, span-60, Tween-80, Poloxamer 188, mannitol, vitamin E, ascorbic acid, methylene chloride, dimethyl sulfoxide, acetonitrile, trifluoroacetic acid. The fine emulsion of mafedine was obtained by ultrasound. The dosage form of mafedine was obtained by freeze drying. Residual solvents were determined by gas chromatography. Quantitative analysis of mafedine was performed by high-performance liquid chromatography. Particle size and zeta potential of emulsion were determined on a Zetasizer Nano ZS.Results and discussion. Lyophilizate of mafedine was obtained and presenting as a light yellow porous, odorless tablet. The average mass of dry tablet was (0,17 ± 0,01) g with mafedine content is (26 ± 1) mg. The water content in the lyophilizate was 3,85 %. The quantity of methylene chloride in the lyophilizate correspond to the requirements for residual solvent content. The reconstitution time of lyophilizate into a primary emulsion was 3–5 seconds. The reconstituted dispersion was yellow, odorless, and did not break within 2 days during storage. The pH of the reconstituted emulsion was 7,34. The average particle size was (164,7 ± 6,4) nm, the zeta potential was –32 mV.Conclusion. The developed dosage form is stable according to its physicochemical and pharmaceutical characteristics and is suitable for experimental study on models as a neuroprotective and neurorehabilitation agent.

Dry Tablet Formulation of PLGA Nanoparticles with a Preocular Applicator for Topical Drug Delivery to the Eye.

To enhance ocular drug bioavailability, a rapidly dissolving dry tablet containing alginate and drug-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles was proposed. For hygienic and easy administration of an accurate drug-dose with this tablet, the use of a preocular applicator was suggested. Herein, a dry tablet was prepared by embedding dexamethasone-loaded PLGA nanoparticles in alginate, which was deposited on the tip of the applicator. The nanoparticles were loaded with 85.45 μg/mg drug and exhibited sustained drug release for 10 h. To evaluate in vivo efficacy, dexamethasone concentration in the aqueous humor was measured after topical administration of the dry tablet, with the applicator, to rabbit eyes and was compared to that achieved with Maxidex®, a commercially-available dexamethasone eye drops. When applied with the preocular applicator, the dry tablet containing alginate could be fully detached and delivered to the eye surface. In fact, it showed up to 2 h of nanoparticle retention on the preocular surface due to tear viscosity enhancement, causing an estimated 2.6-fold increase in ocular drug bioavailability compared to Maxidex®. Therefore, the preocular applicator combined with a dry alginate tablet containing PLGA nanoparticles can be a promising system for aseptically delivering an accurate dose of ophthalmic drug with enhanced bioavailability.

In vivo evaluation of targeted delivery of biological agents using barium sulfate.

This study was aimed to monitor the transit through the intestine by X-ray imaging using barium sulfate (BS) as tracer. The in vitro features of monolithic tablets were correlated with their in vivo behavior in order to provide a tool for the development of targeted formulations containing macromolecular bioactive agents. The impact of BS on various matrices (neutral, ionic) was studied in simulated fluids using the disintegration time (DT) as main parameter. Dry tablets were characterized by spectroscopic methods (X-ray diffraction and Infra-Red) and scanning electron microscopy (SEM). The selected formulations were followed in a beagle dog model. The in vivo and in vitro DT of tablets formulated with BS were compared. Results: anionic excipients carboxymethylcellulose (CMC) and carboxymethylstarch (CMS) protected the active ingredient from the gastric acidity, ensuring its targeted delivery in the intestine. The SEM analysis, before and after transit in simulated fluids, showed that BS remained in the tablets allowing their good follow-up in vivo. The incorporation of 30% protein in tablets with 40% BS had no impact on their behavior. In conclusion, BS and X-ray imagery could be a good alternative to scintigraphy for development of targeted formulations containing high molecular weight bioactive agents.

The Effective Allergenic Reactivity of House Dust Mite Sublingual Immunotherapy Tablets Is Determined by Tablet Formulation.

House dust mite (HDM) sublingual immunotherapy (SLIT) in the form of SLIT-tablets is now an established treatment option for HDM allergy and HDM-induced allergic asthma. In SLIT-tablet immunotherapy allergen extracts are formulated as dry tablets and administered under the tongue where it must be solubilized in saliva in order to be able to interact with the immune system of the sublingual mucosa. Solubilization of the extract must occur within a short time span of about one minute after administration, determined by the sublingual holding time recommended by the manufacturer. Currently, two types of HDM SLIT-tablets are available. Both tablet types contain natural HDM extracts from two common HDM species as the active ingredient, but differ with regard to formulation as one tablet type is based on a freeze-dried tablet formulation while the other is based on a compressed formulation. HDM extracts contain a number of major and minor allergens, which in combination provide the allergenic activity that drives the immunological response and in turn the clinical efficacy of the tablets. Here, a biologically relevant human immunoglobulin E (IgE)-based assay is used to compare the ability of the two HDM SLIT-tablet types to deliver HDM allergenic reactivity from the dry tablet into soluble form. The experiments demonstrate that the freeze-dried formulation delivers HDM allergenic activity into solution faster and more efficiently than the compressed formulation.

The Importance of Tablet Formulation on Allergen Release Kinetics and Efficiency: Comparison of Freeze-dried and Compressed Grass Pollen Sublingual Allergy Immunotherapy Tablet Formulations

PurposeEfficient delivery of allergens to the sublingual mucosa is a prerequisite for successful sublingual immunotherapy (SLIT) for allergy, and in order to become available to immune-competent cells embedded in the sublingual mucosa, allergens need to be delivered in a soluble form. Delivery of solubilized allergens poses a particular challenge for tablet-based allergy immunotherapy, in which allergens are administered under the tongue in the form of dry tablets and need to be dissolved rapidly in a small volume of saliva, with little or no agitation. The purposes of this article were to compare the properties of 2 different pharmaceutical SLIT-tablet formulations, freeze-dried and compressed, and to examine how the tablet formulation affects the efficiency with which allergen is delivered from the dry state of the tablet into soluble form. MethodsTwo SLIT-tablet formulations, both indicated for grass pollen allergic rhinitis and containing grass pollen extract as the active ingredient, were examined with regard to tablet disintegration times, allergen dissolution kinetics, dependency on solvent volume and agitation, and the achieved recovery of the grass allergen content in soluble form with each tablet. FindingsThe freeze-dried and the compressed SLIT-tablet formulations differed markedly with respect to efficiency of allergen release. The freeze-dried tablet disintegrated faster and released grass allergen into solution with a release rate higher than that of the compressed formulation and, in contrast to the compressed formulation, achieved full recovery of the allergen content in soluble form in a small volume of solvent. ImplicationsRapid and complete release of soluble allergen in a small volume of solvent, as demonstrated by the freeze-dried formulation, are key elements of efficient sublingual allergen delivery by SLIT-tablets. Complete allergen release means that the full allergen dose of the tablet is recovered from the tablet and made available to the sublingual immune system in soluble form, and rapid release ensures that the immune system becomes exposed to the highest possible dose of soluble allergen for the maximal duration before swallowing. In contrast, a SLIT-tablet formulation that provides incomplete and slower allergen release will likely require a higher allergen content compared to the more efficient formulation, in order to achieve the same dose of soluble allergen, consequently leading to an excess load of allergen that becomes swallowed without having been made immunologically available.

TECHNOLOGICAL ASPECTS OF TABLETS CREATION BASED ON FLAMMULINA VELUTIPES BIOMASS DRY POWDER

The aim of the work. To study the pharmaco-technological properties of granulate and tablets based on Flammulina velutipes biomass dry powder, to develop the composition and technology of the medication.&#x0D; Materials and Methods. Research of granules and tablets pharmaco-technological properties (sieve analysis, bulk density, tapped density, compressibility index, Hausner ratio, flowability of tablet mass, average weight, resistance to crushing, friability and disintegration of tablets) was carried out in accordance to the requirements of State Pharmacopoeia of Ukraine 2nd edition.&#x0D; Results and Discussion. The determined pharmaco-technological parameters of the granulate indicate good values ​​of the bulk density, tapped density, compressibility index, Hausner ratio and flowability. An intermediate product undergoes a tabletting process to produce a qualitative finished product of satisfactory appearance (plain, cylindrical tablets with a facet, yellowish-white color with brown inclusions, with a height of 4 mm, and diameter of 10 mm), a constant average mass (1.0 g), and strength (68 N).&#x0D; Conclusions. The pharmaco-technological properties of tablet mass (granulate) and Flammulina velutipes biomass dry powder tablets (sieve analysis, bulk density, tapped density, compressibility index, Hausner ratio, flowability, average weight, resistance to crushing, friability and disintegration) were studied. The composition and technology of Flammulina velutipes biomass dry powder tablets have been developed, pharmaco-technological parameters of their quality have been studied, technological block diagram of industrial production has been developed.

Preparation and Use of a Yeast shRNA Delivery System for Gene Silencing in Mosquito Larvae.

The mosquito genome projects facilitated research in new facets of mosquito biology, including functional genetic studies in the dengue and Zika virus vector Aedes aegypti and the primary African malaria vector Anopheles gambiae. RNA interference (RNAi) has facilitated gene silencing experiments in both of these disease vector mosquito species and could one day be applied as a new method of vector control. Here, we describe a procedure for the genetic engineering of Saccharomyces cerevisiae (baker's yeast) that express short hairpin RNA (shRNA) corresponding to mosquito target genes of interest. Following cultivation, which facilitates inexpensive propagation of shRNA, the yeast is inactivated and prepared in a ready-to-use dry tablet formulation that is fed to mosquito larvae. Ingestion of the yeast tablets results in effective larval target gene silencing. This technically straightforward and affordable technique may be applicable to a wide variety of mosquito species and potentially to other arthropods that feed on yeast.

Formation and Application of High Reflectivity Controllable Barium Sulfate Microspheres

This paper investigated the influence of reaction conditions on particle morphology. X-ray powder diffraction (XRD), particle size distribution (PSD), and scanning electron microscopy (SEM) were used to characterize the morphology of barium sulfate. The barium sulfate microspheres were synthesized with BaCl2, Na2SO4, and ethylenediaminetetraacetic acid disodium (EDTA·2Na). The reflectivity of the synthesized barium sulfate microspheres was greater than 99% in the range of 400–700 nm, which was characterized by a reflectance spectrometer. The morphology of the barium sulfate particles and their cross-section were observed by SEM. The prepared microspheres were applied to high-density lipoprotein dry tablets due to their high reflectivity, and the results showed that the prepared tablets had high sensitivity and good repeatability.

A comparative study of the influence of alpha-lactose monohydrate particle morphology on granule and tablet properties after roll compaction/dry granulation

The influence of particle morphology and size of alpha-lactose monohydrate on dry granules and tablets was studied. Four different morphologies were investigated: Two grades of primary crystals, which differed in their particle size and structure (compact crystals vs. agglomerates). The materials were roll compacted at different specific compaction forces and changes in the particle size distribution and the specific surface area were measured. Afterwards, two fractions of granules were pressed to tablets and the tensile strength was compared to that from tablets compressed from the raw materials. The specific surface area was increased induced by roll compaction/dry granulation for all materials. At increased specific compaction forces, the materials showed sufficient size enlargement. The morphology of lactose determined the strength of direct compressed tablets. In contrast, the strength of granule tablets was leveled by the previous compression step during roll compaction/dry granulation. Thus, the tensile strength of tablets compressed directly from the powder mixtures determined whether materials exhibited a loss in tabletability after roll compaction/dry granulation or not. The granule size had only a slight influence on the strength of produced tablets. In some cases, the fraction of smaller granules showed a higher tensile strength compared to the larger fraction.

Headspace gas chromatographic analysis of St John’s Wort (Hypericum perforatum L.) and its medical derivatives

Static headspace gas chromatographic analysis method using flame ionization and mass spectrometric detection was applied for the qualitative and quantitative detection of volatile components in the equilibrium vapor phase of the medicinal St. John's Wort ( Hypericum perforatum L.) plant. The optimal conditions for the gas extraction, producing repeatable and characterizing chromatographic headspace profiles of the St. John's Wort, were established. The retention indices (IiT) for the linear programming of the column temperature with a low-polar stationary phase and the relative areas of the peaks ( A rl,i ) of the St. John's Wort volatile components have been determined. The obtained results were presented in the form of specific headspace-spectra « A rl,i - I i T » of the plants. It has been demonstrated that the headspace spectra of the botanical sample (Samara) and of the three industrial specimens of St. John's Wort obtained from various regions of Russia were close to each other. Major volatile compounds of the Russian St. John's Wort were: ethanal, propanal, dimethylsulfide, 2-methylpropanal, 2-methyl-3-butene-2-ol (marker), 2-methylbuthanal, 2-methyloctane, α-pinene, 3-methylnonane. Current research was the first to suggest using alcohol 2-methyl-3-butene-2-ol ( I i T = 617) as the volatile marker of St. John's Wort. Its relative quantity in the vapor phase of St. John's Wort ( A rl,i ) was equal to 15.53 – 20.75%. It has also been discovered that most of the components of the equilibrium phase of St. John's Wort including the 2-methyl-3-butene-2-ol marker were present in the vapor phase of the St. John's Wort medicines, dry tablet extract of St. John's Wort (Deprim, Slovenia) and oil extract of St. John's Wort (Russia). Keywords : Hypericum perforatum L., medical plant raw material, phytomedicines, volatile organic compounds, gas-liquid chromatography, headspace analysis, chromatographic profile (Russian) DOI: http://dx.doi.org/10.15826/analitika.2018.22.2.002 N.V. Pariichuk 1 , L.A. Onuchak 1 , Iu.A. Arutiunov 1 , V.A. Kurkin 2 , O.E. Pravdivtseva 2 1 Samara National Research University,Moskovskoe sh., 34, Samara, 443086, Russian Federation 2 Samara State Medical University, Chapaevskaia ul., 89, Samara, 443099, Russian Federation

Enhanced dissolution of sildenafil citrate as dry foam tablets

Dry foam formulation technology is alternative approach to enhance dissolution of the drug. Sildenafil citrate was suspended in sodium dodecyl sulfate solution and adding a mixture of maltodextrin and mannitol as diluent to form a paste. Sildenafil citrate paste was passed through a nozzle spray bottle to obtain smooth foam. The homogeneous foam was dried in a vacuum oven and sieved to obtain dry foam granules. The granules were mixed with croscarmellose sodium, magnesium stearate and compressed into tablet. All formulations were evaluated for their physicochemical properties and dissolution profiles. All the tested excipients were compatible with sildenafil citrate by both differential scanning calorimetry (DSC) and infrared (IR) analysis. There are no X-ray diffraction (XRD) peaks representing crystals of sildenafil citrate observed form dry foam formulations. The hardness of tablets was about 5 kg, friability test <1% with a disintegration time <5 min. The sildenafil citrate dry foam tablet had higher dissolution rate in 0.1 N HCl in comparison with commercial sildenafil citrate tablet, sildenafil citrate prepared by direct compression and wet granulation method. Sildenafil citrate dry foam tablet with the high-level composition of surfactant, water and diluent showed enhanced dissolution rate than that of the lower-level composition of these excipients. This formulation was stable under accelerated conditions for at least 6 months.

Evaluation of the tablets’ surface flow velocities in pan coaters

The tablet pan coating process involves various types of transverse tablet bed motions, ranging from rolling to cascading. To preserve satisfactory results in terms of coating quality after scale-up, understanding the dynamics of pan coating process should be achieved. The aim of this study was to establish a methodology of estimating translational surface velocities of the tablets in a pan coater and to assess their dependence on the drum’s filling degree, the pan speed, the presence of baffles and the selected tablet properties in a dry bed system and during coating while varying the drum’s filling degree and the pan speed.Experiments were conducted on the laboratory scale and on the pilot scale in side-vented pan coaters. Surface movement of biconvex two-layer tablets was assessed before, during and after the process of active coating. In order to determine the tablets’ surface flow velocities, a high-speed video of the tablet surface flow was recorded via a borescope inserted into the coating drum and analysed via a cross-correlation algorithm. The obtained tablet velocity data were arranged in a linear fashion as a function of the coating drum’s radius and frequency.Velocity data obtained during coating were close to those of dry tablets after coating. The filling degree had little influence on the tablet velocity profile in a coating drum with baffles but clearly affected it in a coating drum without baffles. In most but not all cases, tablets with a lower static angle of repose had tablet velocity profiles with lower slopes than tablets with higher inter-tablet friction. This particular tablet velocity response can be explained by case specific values of tablet bed’s dynamic angle of repose.

Impact of fillers on dissolution kinetic of fenofibrate dry foams

Dry foam technology reveals the opportunity to improve the dissolution behavior of poorly soluble drugs tending to agglomeration due to micronization. In this study, the impact of fillers on the manufacturability, the properties of dry foams and granules as well as the dissolution kinetics of dry foam tablets was investigated using fenofibrate as a model compound. Different maltodextrins and dried glucose syrups, a maltodextrin–phosphatidylcholine complex, isomalt and a 1:1 mixture of mannitol/glucose syrup were used as filler. Within the group of maltodextrins and glucose syrups, the influences of dextrose equivalent (DE), particle morphology and botanical source of starch were investigated. Comparable macroscopic foam structures were obtained with maltodextrins and glucose syrups whereas different foam morphologies were obtained for the other fillers tested. Regarding the maltodextrins and glucose syrups, different physicochemical and particle properties had a minor impact on granule characteristics and tablet dissolution. Using the maltodextrin–phosphatidylcholine complex resulted in a low specific surface area of the granules and a slow tablet dissolution caused by a slow disintegration. In contrast, a high specific surface area and a fast release were obtained with isomalt and glucose syrup/mannitol mixture indicating that high soluble low molecular weight fillers enable the development of fast dissolving dry foam tablets.

Nanostructured mucoadhesive microparticles for enhanced preocular retention

We describe nanostructured microparticles (NMs) containing a mucoadhesive polymer for enhanced preocular retention and consider them as potential carriers of drugs to the eye. These NMs are each composed of entangled nanofibers to give an enlarged specific surface area, and thus can better adhere to the preocular mucus surface. This physical design allows the microparticles still to be composed mainly of a wall material, poly(lactic-co-glycolic acid), as required for controlled drug delivery, while the effects of an additive, mucoadhesive material, polyethylene glycol, can be synergistically improved via the nanostructured morphology. Thus, when formulated in a dry tablet dosage form, the NMs in this work show more than a 10-fold increase in preocular retention in vivo compared to conventional spherical microparticles. Therefore, we conclude that these mucoadhesive NMs can reside on the preocular surface for a prolonged period, and thus appear to be a promising system for topical drug delivery to the eye.

成人患者におけるL-カルボシステイン（ムコダイン&lt;sup&gt;Ⓡ&lt;/sup&gt;）のドライシロップ剤および錠剤を対象とした服用性に関する調査

成人患者におけるL-カルボシステイン（ムコダイン&lt;sup&gt;Ⓡ&lt;/sup&gt;）のドライシロップ剤および錠剤を対象とした服用性に関する調査

Comparative study on the efficacy of tiotropium bromide inhalation and oral doxofylline treatment of moderate to severe stable chronic obstructive pulmonary disease

This study compared the efficacy and safety of tiotropium bromide inhalation powder (spiriva) and doxofylline oral tablet (doxofylline) in the treatment of chronic obstructive pulmonary disease (COPD). A multi-center, randomized, double-blind, double-dummy, parallel-controlled study involved 127 eligible stable moderate to severe COPD patients treated with inhaled tiotropium dry powder (18 μg/day) or oral doxofylline tablets (0.2 g/time, 2 times a day) for 12 and 24 weeks. Before and after treatment for 12 weeks and 24 weeks, respectively, pulmonary function, 6-min walking distance and dyspnea index were recorded. The results showed that in both tiotropium group and doxofylline groups, after 12-week treatment, FEV(1), FEV(1)/FVC% and 6-min walk distance were significantly higher than those before the medication, while dyspnea index decreased as compared with that before treatment. After 24-week treatment, a slight improvement in the measures was observed as compared with that of 12-weeks treatment, but the difference was not statistically significant. With both 12-week and 24-week treatment, the effect of tiotropium was slightly better than that of doxofylline tablets, with the difference being statistically insignificant. The major adverse events in the tiotropium group and doxofylline group were observed in 9 cases (9.9%) and 12 cases (12.9%), respectively, and no statistically significant difference was found between them. We are led to conclude that both tiotropium at 18 μg a day and doxofylline tablets at 0.2 g/day (two times a day) are effective and safe for the treatment of COPD.