Development and physicochemical characterization of clindamycin resinate for taste masking in pediatrics

Purpose: To evaluate the physicochemical characteristics of clindamycin HCl in a complex form (resinate) with ion exchange resin (IER) (Amberlite IRP69).

Methods: Drug–resin complex was prepared by simple aqueous binding method. Drug binding study was carried out at different drug and resin concentrations. Several physicochemical characterization studies were conducted to evaluate the resinate complex. These studies included flow properties, in vitro drug release in SGF and SIF, DSC, TGA, mass spectroscopy and XPRD evaluations. In addition, stability study of resinate complex was conducted at 25?and 40?°C for up to 1 month.

Results: Clindamycin and Amberlite IRP69 have formed a complex (resinate) and have shown good flow properties, good thermal properties and chemical stability (short term over 4 weeks) at 25 and 40?°C. Clindamycin release profiles from resinate in SGF and SIF have shown immediate release characteristics and release in simulated saliva has shown dependence on water volume.

Conclusion: The clindamycin stable complex with IER (Amberlite IRP69) has the potential for further development as a compatible pediatric liquid formulation (suspension) or a fast disintegrating tablet.     

Development and evaluation of topical films containing phytoestrogenic diaryheptanoids from Curcuma comosa extract

Rational: Phytoestrogens have been found to delay signs of skin aging in post-menopausal women, in a way similar to the effects of estrogens. Diarylheptanoids from a rhizome of traditional Thai herb named Curcuma comosa is considered to be a novel class of phytoestrogens.

Objectives: The aims of this study were to prepare effective topical films using mixed types and vary ratios of hydrophobic (Eudragit RL, Eudragit RS, and Eudragit NE) and hydrophilic polymer (hydroxylpropyl methycellulose, HPMC) with Transcutol as a permeation enhancer for delivery of diarylheptanoids to improve signs of skin aging in post-menopausal women.

Material and methods: Topical films were characterized for their physical and mechanical properties. In vitro release, skin permeation and accumulation were evaluated using Franz diffusion cell and the concentrations of diarylheptanoids were determined using high-performance liquid chromatography.

Results: The combined formulations between HPMC and Eudragit NE showed the satisfactory physical and mechanical properties, and also provided the highest amount of drug released compared to Eudragit RL and Eudragit RS. When the proportion of HPMC amount in the polymer matrix increased, the cumulative drug release also increased (HPMC: Eudragit NE 6:4?>?5:5?>?4:6). Moreover, they provided a high accumulation of diarylheptanoids within skin when using transcutol as a permeation enhancer.

Conclusion: The obtained data provided the skin permeation and accumulation behavior of diarylheptanoids, indicating the feasibility of a skin delivery of the C. comosa extract. The developed films might be topically used as an alternative therapy for protection of skin aging in peri and post-menopausal women.     

Development of a taste-masked oral suspension of clindamycin HCl using ion exchange resin Amberlite IRP 69 for use in pediatrics

Purpose: The purpose of this study is to develop an oral suspension of clindamycin resin complex for the potential use in pediatrics.

Methods: Several types of Ion exchange resins were screened for their binding efficiency with clindamycin. In order to develop a suspension formulation, several thickening agents, surfactants, sweeting, and flavoring agents were evaluated for their influence on the release of clindamycin from resinate. Rheological studies were also conducted to select the optimum amounts of the suspending agents. The release profiles of clindamycin in SGF and SIF were also evaluated from freshly prepared suspension and from suspension formulation after storage for 1 month at 25?°C and 40?°C. Clindamycin bitterness threshold was determined based on volunteers’ evaluation, and taste evaluation was conducted in 12 adult volunteers who evaluated the taste of the optimized suspension against clindamycin solution.

Results: Among all resins tested, Amberlite IRP 69 showed the highest binding efficiency to clindamycin. Several excipients were selected into the suspension formulation based on no or minimum influence on the release of clindamycin from the resinate complex. Moreover, xanthan gum was selected as the optimal suspending agent for the suspension. Clindamycin release profiles in SGF or SIF showed 90% release within 30?min from freshly prepared sample. Clindamycin exhibited good stability profiles at 25?°C and 40?°C over 1 month storage. The mean bitterness threshold of clindamycin was 12.5?μg/ml, and taste evaluation study in adults showed sustainable taste improvement for suspension over clindamycin solution.

Conclusion: Clindamycin/resin complexation has shown to be an efficient method to mask the taste of clindamycin and was developed into a suspension formulation that can be used in pediatrics.     

Reformulation of a codeine phosphate liquid controlled-release product

Background: Ion-exchange resins have been successfully used to create drug formulations providing controlled drug release that are easy to swallow, are sufficiently stable, and have good taste-masking characteristics. The objective of the present study was to replace the ion-exchange resin in a proven delayed release codeine preparation with a new resin able to provide the beneficial properties of the original formulations without the need for Eudragit coating to comply with modern manufacturing regulations. Methods: Nine cationic exchangers with different particle meshes, form, and pore structures were optimally loaded with codeine and their respective in vitro codeine release profiles were compared using the USP XXIII paddle method. Results: The most favorable release profiles were obtained with Amberlite IR 69 F and with Dowex 50 × 8?100. The former was used to prepare the formulated drug–resin complexes as it was available in a pharmaceutically pure form. Both, the cough syrup and concentrate formulations exhibited drug release profiles equivalent to the nonformulated drug–resin complex. These profiles as well as initial free codeine levels, the purity, and the identity were moreover maintained for a storage period of at least 6 months. Conclusion: The in vitro dissolution profiles demonstrated that the use of ion exchanger is most suitable for the development of sustained release codeine formulations.     

Eudragit S100 coated microsponges for Colon targeting of prednisolone

Context: Microsponge is a novel approach for targeting the drug to the colon for the management of colon ailments such as inflammatory bowel disease.

Objective: Prednisolone loaded microsponges (PLMs) were prepared and coated with Eudragit S 100 (ES) and evaluated for colon-specific drug delivery.

Materials and methods: PLMs were prepared using quasi emulsion solvent diffusion technique using ethyl cellulose, triethylcitrate (1% v/v, plasticizer) and polyvinyl alcohol (Mol. Wt. 72?kDa, emulsifying agent). The developed microsponges were compressed into tablets via direct compression technique using sodium carboxymethyl cellulose (Na CMC) and magnesium stearate as super-disintegrant and lubricant, respectively. The tablets were then coated with ES to provide protection against harsh gastric environment and manifest colon-specific drug release.

Results: PLMs were found to be nano-porous spherical microstructures with size around 35?µm and 86% drug encapsulation efficiency. Finally, they were compressed into tablets which were coated with Eudragit S 100 In vitro drug release from ES coated tablets was carried out at various simulated gastrointestinal fluids i.e. 1?hr in SGF (pH 1.2), 2 to 3?h in SIF (pH 4.6), 4–5?h in SIF (pH 6.8), and 6–24?h in SCF (pH 7.4) and the results showed the biphasic release pattern indicating prolonged release for about 24?h.

Discussion and conclusion: In vitro drug release studies revealed that drug starts releasing after 5?h by the time PLMs may enter into the proximal colon. Hence maximum amount of drug could be released in the colon that may result in reduction in dose and dose frequency as well as side effects of drug as observed with the conventional dosage form of prednisolone.     

Synthesis and characterization of photocatalytic polyurethane and poly(methyl methacrylate) microcapsules for the controlled release of methotrexate

Abstract

The aim of this work is to prepare ultraviolet (UV) triggered controlled release of compounds from microcapsule systems (MCs). Polyurethane (PU) and poly(methyl methacrylate) (PMMA) microcapsules were studied with/without chemical functionalization using photocatalytic TiO₂ nanoparticles (NPs) on their surface. Once TiO₂ nanoparticles are illuminated with UV light (λ?=?370?nm), they initiate the rupture of the polymeric bonds of the microcapsule and subsequently initiate the encapsulated compound release, methotrexate (MTX) or rhodamine (Rh), in the present work. The size, polydispersity, charge, and yield of all MCs were measured, being the methotrexate drug release for all systems determined and compared with and without functionalization with TiO₂ NPs, under dark, visible light and UV illumination in vitro. Finally, the Rh release was characterized using fluorescence microscopy. The TiO₂ NPs size is around 10?nm, as determined by X-ray diffraction experiments. The PU MCs average size is around 60?µm, its electric charge +3.11?mV and yield around 85%. As for the PMMA MCs, the average size is around 280?µm, its electric charge ?7.2?mV and yield around 25% and 30% for both MTX and Rh, respectively. In general, adding TiO₂ NPs or the encapsulated products to the MCs does not affect the size but functionalization with TiO₂ NPs lowers the electric charge. Microcapsules functionalized with TiO₂ nanoparticles and irradiated with UV light presented the highest release of MTX and Rh. All other samples showed lower drug release levels when studied under the same conditions.     

Preparation and In Vitro/In Vivo Evaluation of Gliclazide Loaded Eudragit Nanoparticles as a Sustained Release Carriers

ABSTRACT

The aim of this study was to formulate and optimize gliclazide-loaded Eudragit nanoparticles (Eudragit L100 and Eudragit RS) as a sustained release carrier with enhanced efficacy. Eudragit L 100 nanoparticles (ELNP) were prepared by controlled precipitation method whereas Eudragit RSPO nanoparticles (ERSNP) were prepared by solvent evaporation method. The influence of various formulation factors (stirring speed, drug:polymer ratio, homogenization, and addition of surfactants) on particle size, drug loading, and encapsulation efficiency were investigated. The developed Eudragit nanoparticles (L100 and RS) showed high drug loading and encapsulation efficiencies with nanosize. Mean particle size altered by changing the drug:polymer ratio and stirring speed. Addition of surfactants showed a promise to increase drug loading, encapsulation efficiency, and decreased particle size of ELNP as well as ERSNP. Dissolution study revealed sustained release of gliclazide from Eudragit L100 as well as Eudragit RSPO NP. SEM study revealed spherical morphology of the developed Eudragit (L100 and RS) NP. FT-IR and DSC studies showed no interaction of gliclazide with polymers. Stability studies revealed that the gliclazide-loaded nanoparticles were stable at the end of 6 months. Developed Eudragit NPs revealed a decreased t_min (ELNP), and enhanced bioavailability and sustained activity (ELNP and ERSNP) and hence superior activity as compared to plain gliclazide in streptozotocin induced diabetic rat model and glucose-loaded diabetic rat model. The developed Eudragit (L100 and RSPO) NP could reduce dose frequency, decrease side effects, and improve patient compliance.     

Feasibility studies of concomitant administration of optimized formulation of probiotic-loaded Vancomycin hydrochloride pellets for colon delivery

Objective of this study was to develop Vancomycin HCl pellets loaded with Saccharomyces boulardii (S.b.) for pH-dependent system and CODES? for augmenting the efficacy of Vancomycin HCl in the treatment of colitis. Pellets were prepared by extrusion–spheronization. In the pH-dependent system, the pellets were coated with Eudragit FS 30D. These pellets exhibited spherical form and a uniform surface coating. The CODES? system consisted of three components: core containing mannitol, drug and probiotic, an inner acid-soluble coating layer, and an outer layer of enteric coating material. Statistical factorial design was used to optimize both formulations. Scanning electron micrographs of coated pellets revealed uniform coating. In vitro drug release of these coated pellets was studied sequentially in various buffers with (2%) and without rat cecal content for a period of 12?h. From the optimized pH-dependent formulation, F6 (20% w/w coating level and 15% w/v concentration of polymer), higher amount of probiotic was released in earlier time phase (first 5?h) as compared to the CODES? and so R5 [containing acid-soluble inner coating layer (15% w/w coating level and 12% w/v concentration of Eudragit E100), and an outer layer of enteric coating material (12% w/w coating level and 10% w/v concentration of Eudragit L100)] was considered as the best formulation after confirming in vivo X-ray studies conducted on rabbits, suggesting that Vancomycin HCl and S.b. may be co-administered as pellets [CODES?] to enhance the effectiveness of Vancomycin HCl in the treatment of colitis without its associated side effects, which can only be confirmed after clinical trials.     

Development of a topical mupirocin spray for antibacterial and wound-healing applications

Objective: The aim of this study was to develop mupirocin topical spray using Eudragit E100 as a film-forming agent for the treatment of bacterial skin infections as well as to promote wound healing.

Materials and methods: Twenty-seven of mupirocin formulations were formulated containing Eudragit E100 and other excipients. Mupirocin spray was prepared by aerosol crimping and filling machine using HFA-134a as a propellant. The formulations were evaluated for their stability and physicochemical properties. The factorial study was applied to evaluate the effects of glycerol and PEG400 on mupirocin-loaded Eudragit E100 films. The optimized formulation was assessed of drug release, antibacterial activities and in vitro cell line studies in comparison to the ointment formulation.

Results and discussion: Mupirocin sprays were formulated and optimized to obtain the formulation with excellent physicochemical and mechanical properties of the dressing film. The formulation had an excellent stability up to a year with more than 80% of mupirocin content. Mupirocin was released from the film up to 90% within 2?h. The formulation had a potent antibacterial effect against S. aureus and S. epidermidis. The formulation was safe to use as a topical formulation that had no toxicity to keratinocytes, fibroblasts and monocytes. The formulation also had an antiendotoxin effect without stimulating the production of NO and inflammatory cytokines (IL-1β and TNF-α).

Conclusions: Mupirocin topical spray was successful developed as a topical formulation and can be used instead of the ointment formulation. Animal experiments are warranted to further emphasize the safe use in the human skin.     

Film-Coated Enteric Tablet Formulation of Ketorolac Tromethamine

Abstract

A great majority of polymers used for pharmaceutical film-coating purposes have been derivatives of cellulose or methacrylate copolymers (Eudragit series) in most recent studies. The type and frequency of the ester substituents in the chemical structure of these polymers determines their water permeability and pH-solubility characteristics; therefore, different members of the series may be employed for taste-masking or as enteric-coating agents or dissolution rate-controlling membranes in sustained-release dosage forms. Ketorolac tromethamine (KT) is a non-steroidal drug with potent analgesic and anti-inflammatory activity and is absorbed rapidly (T_max < 1.0 hr) with an efficiency of > 87% following oral and intramuscular administration. The most frequent adverse effects occurring with KT are gastrointestinal disturbances such as peptic ulceration and gastrointestinal bleeding. For this reason, enteric-coated film tablets of KT were prepared in this study by the spray technique. Eudragit S-100 and L-100 were selected as coating materials. Polyethylene glycol (PEG) 4000 was used as a plastifying agent. Core tablets of KT were prepared by the direct compression technique. Tablet specifications were determined and evaluated statistically.     

An evaluation of the pharmacokinetics of tiotropium following a single-dose inhalation in healthy subjects using an ultra-sensitive bioanalytical method

Abstract

Objective and significance: The systemic bioavailability of tiotropium following administration via inhalation is known to be very low. A validated ultra-sensitive bioanalytical method with the lowest lower limit of quantitation (LLOQ) was developed and used to evaluate the complete pharmacokinetic profile of tiotropium.

Methods: This was a pharmacokinetic study performed in 18 healthy subjects. Each subject was administered a dose of 18?mcg of tiotropium from a dry powder inhaler (DPI). The subjects’ plasma tiotropium concentrations were assayed with LLOQ of 0.1?pg/mL.

Results: The results showed a mean C_max of 4.98 ± 3.55?pg/mL, and a median (t_max) of 3.6?minutes (range: 1.8–12?minutes). The means for area under the concentration–time curve (AUC) from time zero hours to infinity (AUC_inf) and AUC from time zero hours to the time of the last measurable tiotropium concentration (AUC_t) were 51.11 ± 27.4?pg*h/mL and 37.37 ± 23.38?pg*h/mL, respectively. The mean apparent elimination half-life (t_1/2) was 68.02 ± 24.55?hours. This calculated half-life is longer than what others have reported where a less sensitive LLOQ was used.

Conclusion: The lower LLOQ enabled further insight into the pharmacokinetics of tiotropium that was not possible with other analytical methods. With this method, we were able to quantify tiotropium concentrations as early as one minute following drug administration and up to 144?hours after dosing. The application of this method will allow for studies to be designed properly and enable further investigations into the pharmacokinetics of tiotropium.     

Controlled-Release Theophylline Tablet Formulations Containing Acrylic Resins,II. Combination Resin Formulations

Abstract

Theophylline tablet formulations containing a combination of cationic and anionic acrylic resins were prepared and evaluated. Equal amounts of Eudragit RSPM (cationic resin) and Eudragit L100 (anionic resin) were included at the 15% level (total polymer content) into the tablet formulations. Pressure-hardness profiles with theophylline-resin compacts (4:1) demonstrated that compacts containing the RSPM resin were the most compressible. The dissolution profiles for theophylline in acidic media showed slower release rates from tablets containing the combined resins than from those containing each of the single resins. It was proposed that this decrease in drug release rate was a result of a solid state interaction between the oppositely charged polymers. As the amount of retardant in the matrix increased, the release rates in acidic media decreased. In pH 7.4 phosphate buffer, much faster release was seen due to the higher solubility of the Eudragit L-100 resin at this pH level. Tablet hardness between the range of 6.8 kg to 15 kg showed minimal influences on the dissolution rate. Recompression and relubrication of the tablet formulation containing both polymers, produced a decrease in release rates of theophylline from the tablet matrix.     

Design and development of SMEDDS for colon-specific drug delivery

Abstract

Context: Lipoidal systems have particularly shown potential for specific accumulation in areas with inflamed tissue increasing the selectivity of local drug delivery.

Objective: Formulation and evaluation of self-microemulsifying drug delivery system (SMEDDS) for colon-specific drug delivery for effective treatment of colonic diseases.

Method: Ternary phase diagram was used to optimize level of oil, surfactant and co-surfactant to optimize SMEDDS and were evaluated for percent transmittance, emulsification time, in vitro release, myeloperoxidase (MPO) activity and intestinal accumulation. The spray dried SMEDDS were filled in capsules which were enteric coated with Eudragit S-100 at 10% weight gain to ensure SMEDDS delivery at colon. The spray dried SMEDDS were also evaluated for IR, DSC, XRD, SEM and stability study.

Result: In ternary phase diagram, Capmul MCM C8 and Capmul PG12 NF with surfactant (Tween 20) and co-surfactant (PG) in ratio 2:1 and 3:1, respectively, showed maximum emulsification area. These liquid SMEDDS show maximum transmittance, globule size of 90–30?nm. The spray-dried SMEDDS with diluents show good flow property. The units of MPO activity show lower level as compared to pure drug and control group, histopathology results supports better healing with SMEDDS. This was attributed to accumulation of SMEDDS in inflammatory area as compared to drug which was further proved by accumulation study. Enteric-coated capsule containing SMEDDS are able to deliver drug, specifically at the colonic region.

Conclusion: Higher accumulation of lipoidal drug in inflammatory area and specific release of liposomes by enteric-coated capsules provide better option for the treatment of colonic disease.     

The Release Rate of Indomethacin from Solid Dispersions with Eudragite

Abstract

The coprecipitates were prepared by a solvent technique using Eudragit E as carrier and indomethacin as a model drug.

X-Ray diffractometry, differential scanning calorimetry (DSC) and wettability tests were employed to investigate the physical state of the studied formulations. Up to 50% of indomethacin can be dispersed in an amorphous state in Eudragit E.

The influence of the pH on the in vitro release of solid dispersions has been evaluated. Because of the good solubility of Eudragit E at pH 1.2 a fast dissolution rate of the drug was observed while a marked delay was noticed at pH 7.5 where the polymer is only permeable to water. At pH 5.8 the kinetics of drug release can be modulated by the drug/polymer ratio. The dissolution rate of the drug can be increased by decreasing its amount in the coevaporate.     

Assessment of critical material attributes of polyethylene oxide for formulation of prolonged-release tablets

Abstract

Physicochemical evaluation of polyethylene oxide (PEO) polymers with various molecular weights was performed at molecular (polymeric dispersion) and bulk level (powders, polymeric films, and tablets) with the aim of specifying polymer critical material attributes with the main contribution to drug release from prolonged-release tablets (PRTs). For this purpose, grades of PEO with low, medium, and high viscosity were used for formulating PRTs with a good soluble drug substance (dose solubility volume 15?ml). The results revealed a good correlation (r²=0.88) between in?vivo data (pharmacokinetic parameters: C_max and AUC) and the elastic property of PEO films determined with the nanoindentation method, demonstrating that film level can also be used for the in?vivo prediction of drug dissolution. The study confirmed that polymer molecular weight and its viscosity are the most important critical material attributes affecting drug dissolution (in?vitro) and in?vivo bioavailability (e.g. C_max and AUC). Our research revealed that the nanoindentation technique can distinguish well between various types of polymers, classifying PEO as the most ductile and polyvinyl alcohol as the most brittle. Finally, our study provides an approach for the determination of exact physical attributes of PEO as a critical material attribute from clinically relevant data, and it therefore fulfills the basic principles of product development by Quality by Design.     

In vitro and in vivo effects of morin on the intestinal absorption and pharmacokinetics of olmesartan medoxomil solid dispersions

Abstract

Purpose: In-situ evaluation to corroborate morin effects on the intestinal absorption and pharmacokinetic behavior of freeze-dried OLM-loaded solid dispersions with Caco-2 and in-vivo studies

Methods: Intestinal transport and absorption studies were examined by Caco-2 permeability, in-situ single pass perfusion and closed-loop models along with in-vivo pharmacokinetic studies to evaluate and confirm the effect of P-gp-mediated activity of morin. We evaluated the intestinal membrane damage in the presence of morin by measuring the release of protein and lactate dehydrogenase (LDH) followed by using qualitative and quantitative morphometric analysis to describe the surface characteristics of intestinal epithelium.

Results: Morin showed the highest P_eff value 13.8?±?0.34?×?10^?6?cm/s in jejunum than ileum (p?<?.01) at 100?µM with absorption enhancement of 1.31-fold together with enhanced (p?<?.01) secretory transport of 6.27?±?0.27?×?10?^?6?cm/s in Caco-2 monolayer cells. Our findings noticed 2.37 (in-situ); 2.39 (in-vivo) and 1.43 (in-situ); 1.36 (in-vivo) fold increase in AUC_0–t with elevated C_max and shortened T_max for freeze-dried solid dispersion in the presence of morin as compared to pure OLM and freeze-dried solid dispersions without morin, respectively.

Conclusions: Our study demonstrated that increased solubilization through freeze-dried OLM-loaded solid dispersion together with efflux inhibition improved intestinal permeability to one system that might lead to novel solubilization and efflux pump inhibition as a novel alternative potential to increase oral absorption and bioavailability of OLM.     

Fabrication of novel GMO/Eudragit E100 nanostructures for enhancing oral bioavailability of carvedilol

In the present work, novel nanostructures comprising of glyceryl monooleate (GMO) and Eudragit E100 were prepared using high intensity ultrasonic homogenization. 3² Factorial design approach was used for optimization of nanostructures. Results of regression analysis revealed that the amount of GMO and Eudragit E100 had a drastic effect on particle size and percent entrapment efficiency. Optimized carvedilol-loaded nanostructures (Car-NS) were characterized by FTIR, TEM, DSC, in vitro drug release study. Pharmacokinetic parameters such as C_max, T_max, Ke, Ka, V_d and AUC were estimated for Car-NS upon its oral administration in Sprague-Dawley rats. Particle size of Car-NS was found to be 183?±?2.43?nm with an entrapment efficiency of 81.4?±?0.512%. FTIR studies revealed loading and chemical compatibility of carvedilol with the components of nanostructures. DSC thermograms did not show endothermic peak for melting of carvedilol which could be attributed to solubilization of carvedilol in molten GMO during DSC run. The prepared Car-NS released carvedilol in sustained manner over a period of 10 h as suggested by in vitro drug release study. The pharmacokinetic study of Car-NS showed significant improvement in C_max (two fold, p?p?相似文献   

Evaluation of Chlorpheniramine Maleate microparticles in orally disintegrating film and orally disintegrating tablet for pediatrics

Objective: To mask the bitterness of Chlorpheniramine Maleate via encapsulating drug into Eudragit EPO microparticles, and then incorporate these microparticles into orally disintegrating films (ODF) and orally disintegrating tablets (ODT) for pediatric uses.

Methods: Spray drying of water-in-oil emulsion was utilized to encapsulate Chlorpheniramine Maleate into Eudragit EPO microparticles. Based on an orthogonal experimental design L₉ (3³), polynomial regression models were developed to evaluate correlation between microparticle properties (encapsulation efficiency and drug release) and variables (X₁: weight ratio of polymer to drug, X₂: volume ratio of oil to water and X₃: Q-flow of spray dryer). ODF and ODT formulations were evaluated including weight variation, content uniformity, tensile strength, disintegration time, friability and dissolution profiles. The bitterness taste test was evaluated in 10 adult volunteers.

Results and discussion: From polynomial regression analysis, the best values of variables leading to the optimized microparticles were X₁?=?10, X₂?=?3 and X₃?=?45. The optimized microparticles were incorporated into ODF and ODT with satisfactory weight and drug content uniformity, and acceptable physical strength. Both dosage forms disintegrated immediately (less than 40?s) in simulated saliva solutions. The outcome of taste-masking test indicated that microparticles alleviated drug bitterness significantly; bitterness was not discernible with microparticles incorporated in ODT, whereas only slight bitterness was detected from microparticles incorporated into ODF.

Conclusion: Both ODF and ODT are shown to be suitable vehicles for taste masked Chlorpheniramine Maleate microparticles with potential for pediatric uses.     

Pharmacokinetic properties and bioequivalence of orally inhaled salbutamol in healthy Chinese volunteers

Context: Salbutamol is a short-acting β₂-adrenergic receptor agonist that has been used for many years for relief of bronchospasm. However, studies on the pharmacokinetic profile of orally inhaled salbutamol doses used in clinical practice have not yet been reported in Chinese subjects.

Objective: The aim of this study was to compare the pharmacokinetics and evaluate the bioequivalence of two orally inhaled salbutamol formulations.

Materials and methods: A single-dose randomized fasting two-period, two-treatment and two-sequence crossover open-label bioequivalence study was conducted in 24 healthy Chinese adult male volunteers, with a 1-week washout period between treatments. Plasma concentrations of salbutamol were determined using liquid chromatography coupled to tandem mass spectrometry. Pharmacokinetic parameters, including AUC_0–0.33?h, AUC_0–24?h and C_max were calculated and the 90% confidence intervals of the ratio (test/reference) pharmacokinetic parameters were obtained by analysis of variance on logarithmically transformed data.

Results: The mean (SD) pharmacokinetic parameters of the reference drug were AUC_0–0.33?h, 227.2 (89.9) pg·h/ml; AUC_0–24?h, 2551.9 (1008.0) pg·h/ml; C_max, 801.3 (307.3) pg/ml and t_1/2, 5.14(1.36) h. Those of the test drug were AUC_0–0.33?h, 244.0 (104.4) pg·h/ml; AUC_0–24?h, 2664.4 (1081.8) pg·h/ml; C_max, 873.7 (374.4) pg/ml, t_1/2, 5.29 (1.23) h. The median value for T_max was 0.25?h for both formulations. The 90% confidence intervals for the AUC_0–0.33?h, AUC_0–24?h and C_max were in the range of 0.892–1.208, 0.876–1.195 and 0.911–1.203, respectively.

Conclusion: This single-dose study found that the test and reference products met the regulatory criteria for bioequivalence of China in healthy Chinese volunteers.     

Degradation kinetics of thiamine hydrochloride in directly compressed tablets iii water vapour transmission through free and applied eudragit films

Abstract

Water vapour transmission through free and applied film of four Eudragit resins namely, E₁₀₀, L₁₀₀ and RS₁₀₀ to directly compressed thiamine hydrochloride tablets was investigated. The type of Eudragit film influenced both water vapour transmission and moisture absorption characteristics of the tablets compressed with either single or binary blend of vehicles. The moisture absorption rate constant K_a, for a given batch was found to be a function of vapour pressure, P, and film thickness, L. The relationship between K_a and either of these parameters is exponental and may be expressed as K_a = A exp (x/P) and K_a = K*_a exp (-x*L). In general, film coating with Eudragit resins affected the physical characteristics of the tablets. The rate of drug release, K has an exponentially relationship as K_e K_o exp (-c/L).