Captopril Floating and/or Bioadhesive Tablets: Design and Release Kinetics

Two viscosity grades of hydroxypropylmethylcellulose (HPMC 4000 and 15000 cps) and Carbopol 934P were used to prepare captopril floating tablets. In vitro dissolution was carried out in simulated gastric fluid (enzyme free) at 37°C ± 0.1°C using the USP apparatus 2 basket method. Compared to conventional tablets, release of captopril from these floating tablets was apparently prolonged; as a result, a 24-hr controlled-release dosage form for captopril was achieved. Drug release best fit both the Higuchi model and the Korsmeyer and Peppas equation, followed by first-order kinetics. While tablet hardness and stirring rate had no or little effect on the release kinetics, tablets hardness was found to be a determining factor with regard to the buoyancy of the tablets.     

Development of hollow microspheres as floating controlled-release systems for cardiovascular drugs: preparation and release characteristics

Hollow microspheres of cellulose acetate loaded with four cardiovascular drugs (nifedipine [NFD], nicardapine hydrochloride [NCD], verapamil hydrochloride [VRP], and dipyridamole [DIP]) were prepared by a novel solvent diffusion-evaporation method. The oil-in-water emulsion prepared in an aqueous solution of 0.05% poly(vinyl alcohol) medium with ethyl acetate, a water-soluble and less toxic solvent, was used as the dispersing solvent. The yield of the microspheres was up to 80%. The microspheres had smooth surfaces, with free-flowing and good-packing properties. Scanning electron microscopy (SEM) confirmed their hollow structures, with sizes in the range 489-350 μm. The microspheres tended to float over the gastric media for more than 12 h. The drug loaded in hollow microspheres was in an amorphous state, as confirmed by differential scanning microscopy (DSC). The release of the drugs was controlled for more than 8 h. The release kinetics followed different transport mechanisms depending on the nature of the drug molecules.     

Preparation and evaluation of floating tablets of pregabalin

Abstract

Floating tablets of pregabalin were prepared using different concentrations of the gums (xanthan gum and guar gum), Carbopol 974P NF and HPMC K100. Optimized formulations were studied for physical tests, floating time, swelling behavior, in vitro release studies and stability studies. In vitro drug release was higher for tablet batches containing guar and xanthan gum as compared to the batches containing Carbopol 974P NF. Tablet batches were subjected to stability studies and evaluated by different parameters (drug release, drug content, FTIR and DSC studies). The optimized tablet batch was selected for in vivo pharmacodynamic studies (PTZ induced seizures). The results obtained showed that the onset of jerks and clonus were delayed and extensor phase was abolished with time in treated groups. A significant difference (p?>?0.05) was observed in control and treated group behavior indicating an excellent activity of the formulation for a longer period (>12?h).     

Fabrication and in vitro evaluation of bidirectional release and stability studies of mucoadhesive donut-shaped captopril tablets

Objective: To obtain controlled release of captopril in the stomach, coated, mucoadhesive donut-shaped tablets were designed.

Materials and methods: Donut-shaped tablet were made of different ratios of diluents to polymer or combination of polymers by direct compression method. Top and bottom portions of the tablet were coated with water-insoluble polymer followed by mucoadhesive coating. Time of water penetration, measurement of tensile strength, mucoadhesion studies (static ex vivo and ex vivo wash-off) were taken into account for characterization of respective films. In vitro study has been performed at different dissolution mediums. Optimized batches were also prepared by wet granulation. Stability studies of optimized batches have been performed.

Results: The results of time of water penetration and tensile strength indicated positive response against water impermeation. Mucoadhesive studies showed that film thickness of 0.12?mm was good for retention of tablet at stomach. At pH 1.2, optimized batch of tablet made with hydroxypropyl methyl cellulose (HPMC) E15 as binder showed 80% w/w drug release within 4–5?h with maximum average release of 97.49% w/w. Similarly, maximum average releases of 96.36% w/w and 95.47% w/w were obtained with nearly same dissolution patterns using combination of HPMC E5 and HPMC E50 and sodium salt of carboxy methyl cellulose (NaCMC) 500–600 cPs instead of HPMC E15. The release profiles in the distilled water and pH 4.5 followed the above pattern except deviation at pH 6.8. Stability studies were not positive for all combinations.

Conclusion: Coated, mucoadhesive donut-shaped tablet is good for controlled release of drug in the stomach.     

Optimization and characterization of gastroretentive floating drug delivery system using Box-Behnken design

Context: One among many strategies to prolong gastric residence time and improve local effect of the metronidazole in stomach to eradicate Helicobacter pylori in the treatment of peptic ulcer was floating drug delivery system particularly effervescent gastroretentive tablets.

Objective: The objective of this study was to prepare and evaluate, effervescent floating drug delivery system of a model drug, metronidazole.

Methods: Effervescent floating drug delivery tablets were prepared by wet granulation method. A three-factor, three levels Box-Behnken design was adopted for the optimization. The selected independent variables were amount of hydroxypropyl methylcellulose K 15M (X₁), sodium carboxy methylcellulose (X₂) and NaHCO₃ (X₃). The dependent variables were floating lag time (Y_FLT), cumulative percentage of metronidazole released at 6th h (Y₆) and cumulative percentage of metronidazole released at 12th h (Y₁₂). Physical properties, drug content, in vitro floating lag time, total floating time and drug release behavior were assessed.

Results: Y_FLT range was found to be from 1.02 to 12.07?min. The ranges of other responses, Y₆ and Y₁₂ were 25.72?±?2.85 to 77.14?±?3.42 % and 65.47?±?1.25 to 99.65?±?2.28 %, respectively. Stability studies revealed that no significant change in in vitro floating lag time, total floating time and drug release behavior before and after storage.

Conclusion: It can be concluded that a combination of hydroxypropyl methylcellulose K 15M, sodium carboxy methylcellulose and NaHCO₃ can be used to increase the gastric residence time of the dosage form to improve local effect of metronidazole.     

Evaporation kinetics of volatile liquids and release kinetics of water from a smectite clay: Comparison between experiments and finite element calculations

Numerical calculations of the evaporation kinetics of bulk volatile liquids and of water from smectite clay granules are compared with experimental results. The weight loss of the volatiles is analyzed by thermogravimetry and differential calorimetry. Under the thermodynamic conditions of the experiments, finite element calculations are in good agreement with the experimental data, and an approximate semi-analytical model is developed in order to explain the dependence of the rate of evaporation on the temperature, the chemical species and the carrier gas flow rate. The initial rate of evaporation of water from the clay granule is close to that for bulk water. Its decrease with time is determined mainly by changes in the gas/condensed phase partition given by the equilibrium desorption isotherm, with little limitations due to internal diffusion effects for the present experimental conditions. Its temperature dependence could also be approximately described by an Arrhenius-type equation derived from the semi-analytical model. Further analysis of the experimental measurements reveals steps in the heat of vaporization of water as a function of water concentration, that could be related to the equilibrium desorption isotherm.     

Drug release kinetics from tablet matrices based upon ethylcellulose ether-derivatives: a comparison between different formulations

The present study involved the preparation of ibuprofen-containing controlled release tablets formulated from either the established granular product, Ethocel®Standard Premium, or the novel finely-milled product, Ethocel®Standard FP Premium. The tablets were prepared by either direct compression or wet granulation. The aim was to explore the influence of different parameters on the kinetics and mechanisms of ibuprofen release from the tablets. These parameters were; polymer particle size, polymer molecular weight, drug : polymer ratio, preparation methodology and partial replacement of lactose with the coexcipient—hydroxypropyl methylcellulose (HPMC). The derived drug release data were analyzed with reference to various established mathematical models while the f₂-metric technique was used in order to determine profile equivalency. It was found that drug release was mostly modulated by several interactive factors apparently exhibiting crosstalk. Nevertheless, it was possible to identify some simple rules. Incorporation of Ethocel® FP polymers and application of the wet granulation technique facilitated greater efficiency in controlling ibuprofen release behavior from the matrices. Furthermore, drug release profiles could be modulated by partial substitution of the primary excipient with HPMC. Polymer concentrations and particle sizes, rather than viscosity grade, were found to be decisive factors in controlling drug release rates.     

Hydrothermal processing on potassic syenite powder: Zeolite synthesis and potassium release kinetics

To make potassium accessible to agricultural application from K-silicates, processing on potassic syenite powder under mild alkaline hydrothermal conditions was conducted, as a result of which, potassium became accessible into solution, and to two zeolite powders (analcime and hydroxycancrinite) were successfully obtained. A scale-up operation in 25L-hydrothermal reactor supported the feasibility of further industrial implementation. The kinetic model derived from geochemical study was adopted to describe K⁺ release behavior, and two kinetic factors, reaction order and apparent activation energy, over temperature range of 477–531 K were 2.61 and 46.61 kJ/mol. The concentrated alkaline solution giving rise to higher reaction order and lower apparent activation energy was a dominated factor accelerating K-feldspar dissolution accomplished within hours. The hydrothermal approach proposed in this work is a simplified and green chemical way for the comprehensive utilization of K-silicates.     

Preparation and evaluation of floating risedronate sodium-Gelucire 43/01 formulations

Single and multi-unit floating matrices of risedronate sodium were prepared using Gelucire® 43/01 by melt solidification and melt granulation technique, respectively. The controlled release floating matrices were evaluated for in vitro and in vivo floating ability and in vitro drug release. Effect of aging on Gelucire® 43/01 was evaluated by hot stage microscopy (HSM), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), in vitro floating ability, and in vitro drug release. Multi-unit system obtained has shown initial burst release, which was suppressed in single unit system. Both single- as well as multi-unit systems showed increase in rate of drug release on aging due to changes in the properties of the Gelucire® 43/01. Multi-unit matrices obtained by melt granulation were relatively easier for scale up and advantageous if the initial burst release does not cause any significant clinical adversity.     

Development of Hollow Microspheres as Floating Controlled-Release Systems for Cardiovascular Drugs: Preparation and Release Characteristics

Hollow microspheres of cellulose acetate loaded with four cardiovascular drugs (nifedipine [NFD], nicardapine hydrochloride [NCD], verapamil hydrochloride [VRP], and dipyridamole [DIP]) were prepared by a novel solvent diffusion-evaporation method. The oil-in-water emulsion prepared in an aqueous solution of 0.05% poly(vinyl alcohol) medium with ethyl acetate, a water-soluble and less toxic solvent, was used as the dispersing solvent. The yield of the microspheres was up to 80%. The microspheres had smooth surfaces, with free-flowing and good-packing properties. Scanning electron microscopy (SEM) confirmed their hollow structures, with sizes in the range 489–350 μm. The microspheres tended to float over the gastric media for more than 12 h. The drug loaded in hollow microspheres was in an amorphous state, as confirmed by differential scanning microscopy (DSC). The release of the drugs was controlled for more than 8 h. The release kinetics followed different transport mechanisms depending on the nature of the drug molecules.     

Comparing the mucoadhesivity and drug release mechanisms of various polymer-containing propranolol buccal tablets

The aims were to compare the mucoadhesivity, controlled release properties, and release mechanisms of several polymeric systems of propranolol buccal tablets and to propose polymer(s) for formulation optimization. Mucoadhesivity differences in the polymer ranking between compacts and tablets were found. Mathematical models that best described the matrices were power law or a combination of the power law and Hopfenberg models. Poly acrylic acid (PAA), carboxymethyl cellulose (CMC), and poly ethylene glycol (PEG) in combination, were identified as suitable polymers for formulation optimization of a multipolymeric propranolol buccal tablet. Artificial neural networks were employed as a confirmatory approach to explicate that the selected polymers, in particular PAA, produced the most significant effect on the mean dissolution time and mucoadhesivity.     

Thermal sintering: a novel technique used in the design,optimization and biopharmaceutical evaluation of propranolol HCl gastric floating tablets

The objective of the present investigation was to study the applicability of thermal sintering technique for the development of gastric floating tablets of propranolol HCl. Formulations were prepared using four independent variables, namely (i) polymer quantity, (ii) sodium bicarbonate concentration, (iii) sintering temperature and (iv) sintering time. Floating lag time and t₉₅ were taken as dependent variables. Tablets were prepared by the direct compression method and were evaluated for physicochemical properties, in vitro buoyancy and dissolution studies. From the drug release studies, it was observed that drug retarding property mainly depends upon the sintering temperature and time of exposure. The statistically optimized formulation (PTSso) was characterized by Fourier transform infrared spectroscopy and differential scanning calorimetry studies, and no significant chemical interaction between drug and polymer was observed. Optimized formulation was stable at accelerated conditions for a period of six months. PTSso was evaluated for in vivo buoyancy studies in humans for both fed and fasted states and found that gastric residence time of the floating tablets were enhanced by fed stage but not in fasted state. Optimized formulation PTSso and commercial formulation Ciplar LA 80 were subjected to bioavailability studies in healthy human volunteers by estimating pharmacokinetic parameters such as C_max, T_max, area under curve (AUC), elimination rate constant (K_el), biological half-life (t_1/2) and mean residence time (MRT). There was a significant increase in the bioavailability of the propranolol HCl from PTSso formulation, which was evident from increased AUC levels and larger MRT values than Ciplar LA 80.     

V-POSS/UPR非等温固化动力学与物理性能

为了提高不饱和聚酯树脂(UPR)的性能,本文中以乙烯基笼型倍半硅氧烷(V-POSS)改性不饱和聚酯树脂,用非等温 DSC法研究了UPR和5% V-POSS/UPR体系的固化反应动力学以及表观反应活化能与转化率之间的关系,测定了玻璃钢层压板的力学性能和电性能。结果表明,加入V-POSS固化反应E_a随反应程度增加而降低,通过使用两参数Šesták-Berggren(S-B)模型描述固化反应过程,得到了反应动力学方程。当V-POSS质量分数为5%时玻璃钢层压板拉伸强度达到最大值,提高了17.6 MPa,冲击强度随V-POSS加入量增加而降低,但在10%时冲击强度有所上升。层压板电性能随 V-POSS加入量增加而提高,其中体积电阻率和表面电阻率提高1～2个数量级。     

Binary nanocomposite of Fe3O4/MWCNTs for adsorption of Reactive Violet 2: Taguchi design,kinetics and equilibrium isotherms

Binary nanocomposite of magnetite/multi-walled carbon nanotubes (Fe₃O₄/MWCNTs) was synthesized through the chemical reduction method at room temperature and employed for adsorptive removal of Reactive Violet 2 (RV2) from aqueous solutions. The experiments were carried out based on a Taguchi experimental design with four variables of the adsorbent dosage, pH, contact time and ionic strength. Analysis of variance (ANOVA) showed that the adsorbent dosage with contribution of 79.14% was the most effective factor on the process efficiency. Percent contributions of solution pH and contact time were found to be 9.85 and 6.16, respectively. The ionic strength showed no considerable contribution to the response. The optimal dye removal conditions were determined as the adsorbent dosage of 2.0?g?L^?1, pH = 6, contact time of 30?minutes and ionic strength of 0.1?mol?L^?1 which resulted in the average efficiency of 98.23% for RV2 removal. The results showed that RV2 adsorption onto Fe₃O₄/MWCNTs followed the pseudo-second order kinetic model. Moreover, the intraparticle diffusion model suggested a two-step adsorption process, including macropore diffusion of about 94% of RV2 molecules into the nanocomposite surface during ～10?minutes and a micropore diffusion as the rate-limiting step. Fitting of the experimental data to six isotherms (Langmuir, Harkins-Jura, Freundlich, Tempkin, Halsey and Redlich-Peterson) was also investigated and Redlich-Peterson and Halsey isotherms provided the best quality of fitting for the dye-nanocomposite system with R² values of 0.9992 and 0.9906, respectively.     

制备方法对高分子载药涂层结构和体外释放动力学的影响

分别采用浸涂法和喷涂法在316L不锈钢基体表面制备含雷帕霉素的丙烯酸树脂缓释涂层,并使用FTIR、SEM及DSC对涂层中雷帕霉素的物化状态进行了测试和分析,测试了上述两种方法制备的药物洗脱支架的体外药物释放动力学曲线,并分析了两种制备方法之间的差异.结果表明上述两种方法制备的含药涂层药物分布状态存在一定差异,药物释放速率有所不同,以浸涂法制备的含药涂层释放速率更快.     

The contributions of erosion, swelling, and porosity to theophylline release kinetics from Cissus populnea polymer matrices

The variable factors of erosion rate, swelling rate, and porosity were used in studying the release patterns of theophylline from our Cissus populnea polymer (CPP) matrices under the different factor combinations given by a simple 2ⁿ factorial experimental design. The zero-order slopes and correlation coefficients representing release rate and linearity, respectively, as obtained from both the nonsteady state and steady state were statistically treated. It appears that the nonsteady-state analysis is more suitable for studying the effects of individual factors, while the steady-state analysis appears more suitable for studying interaction effects of the factors. The study also showed that erosion is the main mechanism by which theophylline is released from the matrices, while swelling is responsible for maintaining linearity in the zero-order release curves. A careful examination of the statistical results shows some functional relationships between the factors, which should be considered in designing more detailed factorial experiments to enable the establishment of equation models for predicting the release profile of theophylline from our CPP matrices under any given dissolution condition.     

Systematic development of pH-independent controlled release tablets of carvedilol using central composite design and artificial neural networks

The purpose of this study was to apply the optimization method incorporating artificial neural network (ANN) using pH-independent release of weakly basic drug, carvedilol from HPMC-based matrix formulation. Because of weakly basic nature of carvedilol, drug shows pH-dependent solubility. The enteric polymer EUDRAGIT L100 was added formulations to overcome pH-dependent solubility of carvedilol. Effects of the Hydroxypropylmethyl cellulose (HPMC) K4M and EUDRAGIT L100 amount on drug release were investigated. For this purpose 13 kinds of formulations were prepared at three different levels of each variables. The optimization of the formulation was evaluated by using ANN method. Two formulation parameters, the amounts of HPMC K4M and Eudragit L100 at three levels (?1, 0, 1) were selected as independent/input variables. In-vitro dissolution sampling times at twelve different time points were selected as dependent/output variables. By using experimental dissolution results and amount of HPMC K4M and EUDRAGIT L100, percentage of dissolved carvedilol was predicted by ANN. Similarity factor (f₂) between predicted and experimentally observed profile was calculated and f₂ value was found 76.33. This value showed that there was no difference between predicted and experimentally observed drug release profile. As a result of these experiments, it was found that ANNs can be successfully used to optimize controlled release drug delivery systems.     

Spray-drying as a method for microparticulate controlled release systems preparation: advantages and limits. I. Water-soluble drugs

Spray-drying was used for the preparation of paracetamol/eudragit RS or RL or ethylcellulose microspheres to verify the possibility of their use in controlled-release solid-dosage forms formulation and try to determine advantages and limits of the technique of such use. Microspheres were first characterized by scanning electron microscopy, differential scanning calorimetry, x-ray diffractometry, and in vitro dissolution studies and then used for the preparation of tablets. During this step, the compressibility of the spray-dried powders was also evaluated. In vitro dissolution studies were performed also on the tablets and their release control was accessed. Although powders were unable to slow down drug release, tablets obtained from microsphere compression showed a good capability of controlling paracetamol release when eudragit RS or ethylcellulose was used, even at low polymer amounts.     

Crystallization kinetics and martensitic transformation of Ti49Ni46.5Ce4.5 alloy thin film

The Ti₄₉Ni_46.5Ce_4.5 alloy thin film was prepared by direct current (DC) magnetron sputtering system for the first time. Crystallization kinetics, phase composition and the behaviors of martensitic transformation were studied. The results by X-ray diffraction (XRD) and differential scanning calorimeter (DSC) demonstrated that the primary second phase of TiNiCe alloy thin films was Ce₂Ni₇ phase, apparent activation energy was determined to be 510 kJ/mol at the continuous heating process, Avrami exponents for different isothermal temperature were in the range of 1.1-1.88 between 713 and 730 K, one-step martensitic transformation was observed in the crystallized Ti₄₉Ni_46.5Ce_4.5 alloy thin films. The influence of thermal process on martensitic transformation temperature was investigated with non-isothermal and isothermal crystallization. The reason behind the transformation temperature change was also discussed.     

改性黄原胶/膨润土复合树脂对Cu2+的吸附热力学与动力学研究

以2-丙烯酰胺基-2-甲基丙磺酸(AMPS)和丙烯酸(AA)为单体,利用水溶液聚合法制备了改性黄原胶/膨润土复合树脂。研究了复合树脂对Cu2+的静态吸附行为,并分析了其吸附热力学和动力学特征。采用红外光谱仪(FT-IR)和X射线衍射仪(XRD)对复合树脂及吸附产物结构进行了表征。结果表明:在303K、313K和323K温度下,复合树脂对Cu2+吸附等温线同时符合Langmuir和Freundlich等温方程,吸附是一个自发的吸热过程,吸附行为可以用二级吸附动力学模型来描述,吸附后复合树脂的结晶能力下降。