hGH release from directly compressed hGH-PLGA biodegradable implantable tablets: Influence of physicomechanical factors

The incidence of compression conditions, porosity and polymer degradation on human growth hormone (hGH) release from PLGA implantable tablets was evaluated with the aim of gaining insight in the mechanism involved in drug delivery from biodegradable matrices. Tablets elaborated by direct compression of hGH with PLGA, applying various compression forces for different times, kept the integrity and the stability of the hormone. Tablet dimensions, viscoelastic properties, glass to rubber transition temperature (T_g), PLGA degradation rate and water uptake were analyzed in the freshly prepared implantable tablets as well as at several times during release test in phosphate buffer pH 7.4. Placebo tablets were also prepared to evaluate the incidence of hGH on the physicomechanical properties of the device and PLGA degradation rate. Porosity remarkably determined the amount of hGH released, through an effect on the easiness of water penetration in the tablet and on the beginning of PLGA degradation. The decrease in PLGA molecular weight during the first days in the release medium, despite of being minor, significantly conditioned hGH release rate. The more dramatic changes in PLGA molecular weight observed after 20 days in the release medium notably reduced the T_g and the viscous and elastic moduli of the tablets. The overall analysis of the events underwent by the tablets in contact with the aqueous medium was used to explain the drug release profile and may help to optimize the design of the PLGA-based implantable tablets as peptidic drug delivery systems.     

Relationship between diffusivity of water molecules inside hydrating tablets and their drug release behavior elucidated by magnetic resonance imaging

We reported previously that sustained release matrix tablets showed zero-order drug release without being affected by pH change. To understand drug release mechanisms more fully, we monitored the swelling and erosion of hydrating tablets using magnetic resonance imaging (MRI). Three different types of tablets comprised of polyion complex-forming materials and a hydroxypropyl methylcellulose (HPMC) were used. Proton density- and diffusion-weighted images of the hydrating tablets were acquired at intervals. Furthermore, apparent self-diffusion coefficient maps were generated from diffusion-weighted imaging to evaluate the state of hydrating tablets. Our findings indicated that water penetration into polyion complex tablets was faster than that into HPMC matrix tablets. In polyion complex tablets, water molecules were dispersed homogeneously and their diffusivity was relatively high, whereas in HPMC matrix tablets, water molecule movement was tightly restricted within the gel. An optimal tablet formulation determined in a previous study had water molecule penetration and diffusivity properties that appeared intermediate to those of polyion complex and HPMC matrix tablets; water molecules were capable of penetrating throughout the tablets and relatively high diffusivity was similar to that in the polyion complex tablet, whereas like the HPMC matrix tablet, it was well swollen. This study succeeded in characterizing the tablet hydration process. MRI provides profound insight into the state of water molecules in hydrating tablets; thus, it is a useful tool for understanding drug release mechanisms at a molecular level.     

Wetting behaviour,moisture up-take and electrokinetic properties of lignocellulosic fibres

The wetting and moisture up-take behaviour, as well as the electrokinetic properties of various lignocellulosic fibres were characterised. Knowledge of surface and water uptake properties of this kind of materials will help to tailor their potential use in different end user applications. The surface tension of the fibres was determined from wetting measurements using the capillary rise technique. The wetting data were used to determine the surface tension of the fibres. Our results show that the surface tension of the lignocellulosic fibres is a linear function of their cellulose content. Zeta-potential measurements were exploited to characterise the surface chemistry of the fibres. Measuring the zeta-potential as function of time enables the rapid assessment of the water up-take, i.e. the swelling behaviour of the fibres. The results obtained by the zeta potential measurements correlate, with the exception of flax, in a linear manner with the results obtained from conventional moisture uptake measurements. Even though all lignocellulosic fibres are very hydrophilic due to the presence of polar oxygen containing groups they have different grades of hydrophilicity, which is also reflected in the different water uptake capabilities measured. The wetting, moisture uptake and electrokinetic properties of the lignocellulosic fibres are determined by the availability of the surface functional groups present, which is usually consequence of the processes used to separate, and extract the fibres from the plant (retting), as well as any further processing used to improve the fibre quality.     

Studies of rapidly disintegrating tablets in the oral cavity using co-ground mixtures of mannitol with crospovidone

We attempted the development of rapid oral disintegration tablets by direct compression using co-ground mixture of D-mannitol and crospovidone. The co-ground mixture was prepared with a vibration rod mill. The tablets were formed by compression using a single punch-tableting machine after addition of the co-ground mixture to non-ground D-mannitol, crospovidone and magnesium stearate. Regarding the properties of tablets, hardness and the time of disintegration were measured. The particle diameter and specific surface area of the co-ground mixture were measured. The tablets manufactured from a physical mixture of 30% (w/w) co-ground mixture of D-mannitol and crospovidone (mixed ratio 9 :1) with 65.5% (w/w) of non-ground mannitol, 4% (w/w) of crospovidone, and 0.5% (w/w) of magnesium stearate had good properties for rapidly disintegrating tablets in the oral cavity. They showed the hardness of 4.9 kg and disintegration time of 33 s. We found that adding co-ground mixture of D-mannitol and crospovidone is useful in enhancing hardness of the tablets that could not be achieved by addition of their individually ground mixture. The improvement in the hardness of the tablets was also observed when other saccharides and disintegrants were used. This method was proved to be applicable in the manufacture of tables of ascorbic acid, a water-soluble drug and nifedipine, a slightly water soluble drug; and the dissolution rate of nifedipine from the tablets in water was remarkably improved. The particle sizes of D-mannitol in the co-ground mixture were smaller than that of the individually ground mixture, resulting in a larger specific surface area of the co-ground mixture than that of the individually ground mixture. Therefore, it was presumed that crospovidone acted as a grinding assistant for D-mannitol in the co-grinding process, enhancing the hardness of tablets by increasing the contact area among powder particles.     

Investigation of water mobility and diffusivity in hydrating micronized low-substituted hydroxypropyl cellulose,hydroxypropylmethyl cellulose,and hydroxypropyl cellulose matrix tablets by magnetic resonance imaging (MRI)

The water mobility and diffusivity in the gel-layer of hydrating low-substituted hydroxypropyl cellulose (LH41) tablets with or without a drug were investigated by magnetic resonance imaging (MRI) and compared with those properties in the gel-layer of hydroxypropylmethyl cellulose (HPMC) and hydroxypropyl cellulose (HPC) tablets. For this purpose, a localized image-analysis method was newly developed, and the spin-spin relaxation time (T(2)) and apparent self-diffusion coefficient (ADC) of water in the gel-layer were visualized in one-dimensional maps. Those maps showed that the extent of gel-layer growth in the tablets was in the order of HPC>HPMC>LH41, and there was a water mobility gradient across the gel-layers of all three tablet formulations. The T(2) and ADC in the outer parts of the gel-layers were close to those of free water. In contrast, these values in the inner parts of the gel-layer decreased progressively; suggesting that the water mobility and diffusivity around the core interface were highly restricted. Furthermore, the correlation between the T(2) of (1)H proton in the gel-layer of the tablets and the drug release rate from the tablets was observed.     

Water absorption and degradation characteristics of chitosan-based polyesters and hydroxyapatite composites

Blends of chitosan and biodegradable synthetic aliphatic polyesters (polycaprolactone, poly(butylene succinate), poly[(butylene succinate)-co-adipate], poly[(butylene terephthalate)-co-adipate], and poly(lactic acid)) were injection-molded. These samples were immersed in isotonic solution at 37 degrees C for a period of 60 d. The water uptake and the degradation properties, as measured by the loss in tensile strength, were evaluated as a function of time. In this study, the rate and the equilibrium water uptake were proportional to the amount of chitosan in the blend. The addition of HA to chitosan and polyester significantly reduced the equilibrium water uptake. The water uptake did not follow the classical Fickian phenomena and could be expressed by a two-stage sorption non-Fickian diffusion model. Contact angle measurement was used to quantify the changes in surface hydrophilicity as a function of chitosan and polyester composition. The glycerol contact angle decreased with increasing synthetic components in the blend. The blends and composites also showed increased degradation, as quantified by a loss in their mechanical properties, with increase in natural content. The degradation of properties was directly related to the water uptake of the blends; the higher the water uptake, the higher the degradation. Pure polyesters, while having low water uptake, nevertheless showed significant degradation by a precipitous drop in the strain at break. Among the polyesters, poly(lactic acid) displayed maximum degradation, while polycaprolactone displayed the least.     

Effect of pulverization of the bulk powder on the hydration of creatine anhydrate tablets and their pharmaceutical properties

The hydration behavior and expansion properties of untreated and pulverized creatine anhydrate (CRA) tablets were studied under 60 and 75%RH at 25 degrees C by using differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD). The tablet hardness of untreated and pulverized CRA tablets was significantly decreased after hydration. There was a linear relationship between the degree of hydration and the tablet hardness of untreated CRA tablets compressed at 1000 kg/cm2. In contrast, the relationship between the degree of hydration and the tablet hardness of pulverized CRA tablets was nonlinear. These results suggest that the reduction in hardness of pulverized CRA tablets does not depend solely on the hydration level of crystal water. PXRD analysis indicated that the diffraction pattern of the pulverized CRA powder was similar to that of the untreated CRA powder. However, the diffraction intensity of the pulverized CRA powder was slightly lower than that of the untreated CRA powder at high angle. The micropore radius of both untreated and pulverized CRA tablets was significantly increased after hydration, but analysis of the relationship between micropore radius and fractional hydration of crystal water showed that untreated CRA tablets were more affected than pulverized CRA tablets. Therefore, the reduction in tablet hardness depends not only on the hydration behavior but also on the crystal orientation of the CRA powder.     

Determination of Vitamin B12 in Multivitamin Tablets by High Performance Liquid Chromatography

Abstract

Two procedures for separation and determination of vitamin B₁₂ in multivitamin tablets by reversed phase high performance liquid chromatography are proposed. Sample preparation is very simple: tablets are dissolved in distilled water, centrifuged and filtered. The sample solution is directly applied in the sample loop injector and chromatograms are obtained with gradient elution using water-methanol and water-acetonitrile as solvents. The peak of vitamin B₁₂ from samples of B-complex tablets is well separated with the two procedures. For multivitamin tablets, however, only the procedure with water and methanol as solvents was good for separation and quantification of vitamin B₁₂. Both procedures were verified by the standard addition method and also compared to a previously developed method using electrothermal atomic absorption spectrometry for vitamin B₁₂ determination.     

High throughput sonication: evaluation for compound solubilization

Dissolution of organic compounds in DMSO in HTS plate or tube format is a difficult problem as users move to higher compression plate formats. Precipitation of compounds from DMSO screening stocks is a recognized problem in the HTS materials management process. The adverse effect of freeze thaw cycles on DMSO stock solutions stored in plate format as a result of cherry picking operations has led to the gradual replacement of plate-based storage with tube-based storage so as to minimize the number of freeze thaw cycles. Compound solubility in DMSO is markedly decreased by uptake of small quantities of water. We attribute this effect to the non ideal properties of DMSO water mixtures such that cavity formation in solvent, a necessary step in dissolution, is more difficult in wet DMSO than in dry DMSO or in pure water. We report here that efficient compound dissolution is possible even in 384 well format by the use of in-well plate-based sonication. Surprisingly, compounds precipitated from DMSO stocks either by water uptake or repeated freeze thaw cycles can be re-dissolved by low energy sonication. Finally, we demonstrate that precipitation of compound from DMSO stock solutions is synergistically enhanced by water uptake into DMSO compound stock solutions as well as by increasing the number of freeze thaw cycles.     

Wastes from Wood Extraction Used in Composite Materials: Behavior after Accelerated Weathering

New materials were obtained by incorporating in polypropylene (PP) matrix 60% wood wastes resulting after extraction with supercritical carbon dioxide, water, and ethanol. Structural, mechanical, thermal, and rheological characterizations, as well as moisture uptake of the composites, were evaluated before and after accelerated weathering. It was found that the extraction method influenced the composite properties due to the hydrophilic-hydrophobic balance. The addition of extracted fibers results in an increase in hardness and tensile properties and a decrease of impact strength as compared to PP.     

Control of water-channel structure and state of water in sulfonated poly(arylene ether sulfone)/diethoxydimethylsilane in situ hybridized proton conductors and its influence on transport properties for DMFC membranes

A new approach for noticeably improving the DMFC membrane transport properties of sulfonated poly(arylene ether sulfone) copolymers (SPAES) has been demonstrated, which is based on controlling the water-channel structure and the state of water by in situ hybridization of ORMOSIL (Organically Modified SILicates). Diethoxydimethylsilane (DEDMS) was employed as a functional ORMOSIL precursor. Its hydrophobic nature made it possible to adjust the hydrophilicity of the resulting hybrid membranes. An increase of DEDMS uptake into SPAES membranes allowed the water uptake to decrease and the water channels to become narrow and tortuous. The influence of DEDMS uptake on the state of water was investigated by measuring the characteristic melting peak of water at 0 °C. Based on this investigation, the dependence of water uptake on the state of water was quantitatively identified. A noteworthy observation is that the incorporation of DEDMS into SPAES was effective in suppressing the methanol crossover with slightly sacrificing the proton conductivity, resulting in the higher selectivity. This improvement in DFMC membrane transport properties was discussed in terms of the water-channel structure and the state of water.     

In vitro evaluation of mucoadhesive vaginal tablets of antifungal drugs prepared with thiolated polymer and development of a new dissolution technique for vaginal formulations

The main objective of this work was to develop antifungal matrix tablet for vaginal applications using mucoadhesive thiolated polymer. Econazole nitrate (EN) and miconazole nitrate (MN) were used as antifungal drugs to prepare the vaginal tablet formulations. Thiolated poly(acrylic acid)-cysteine (PAA-Cys) conjugate was synthesized by the covalent attachment of L-cysteine to PAA with the formation of amide bonds between the primary amino group of L-cysteine and the carboxylic acid group of the polymer. Vaginal mucoadhesive matrix tablets were prepared by direct compression technique. The investigation focused on the influence of modified polymer on water uptake behavior, mucoadhesive property and release rate of drug. Thiolated polymer increased the water uptake ratio and mucoadhesive property of the formulations. A new simple dissolution technique was developed to simulate the vaginal environment for the evaluation of release behavior of vaginal tablets. In this technique, daily production amount and rate of the vaginal fluid was used without any rotational movement. The drug release was found to be slower from PAA-Cys compared to that from PAA formulations. The similarity study results confirmed that the difference in particle size of EN and MN did not affect their release profile. The release process was described by plotting the fraction released drug versus time and n fitting data to the simple exponential model: M(t)/M(∞)=kt(n). The release kinetics were determined as Super Case II for all the formulations prepared with PAA or PAA-Cys. According to these results the mucoadhesive vaginal tablet formulations prepared with PAA-Cys represent good example for delivery systems which prolong the residence time of drugs at the vaginal mucosal surface.     

Application of nilvadipine solid dispersion to tablet formulation and manufacturing using crospovidone and methylcellulose as dispersion carriers

Nilvadipine (NIL) solid dispersion using crospovidone (Cross-linked-N-vinyl-2-pyrolidone, cl-PVP) and methylcellulose (MC) as carriers was applied to tablet formulation. Several grades of cl-PVP and MC were used, and their influence on tablet properties such as hardness, disintegration, dissolution and chemical stability were investigated. The agitation granulation method was used for preparation of solid dispersion granules, and the granules were compressed using a rotary tableting machine, and finally the obtained tablets were coated with film. As the particle size of cl-PVP decreased, hardness and apparent solubility were increased, while dissolution rate was lowered. When a higher viscosity grade of MC was used, hardness and dissolution rate were increased, and apparent solubility did not change. All batches of tablets were chemically stable at 40 degrees C, 75% relative humidity (R.H.) for six months. Finally, tablets with enhanced dissolution properties were obtained by using Polyplasdone XL-10 and Metolose SM-25 as the grades of cl-PVP and MC, respectively. These formulation tablets showed higher solubility and dissolution rate during storage as well as initial indicating good physical stability.     

Preparation of antipyretic analgesic by direct compression and its evaluation

Direct compression is able to produce tablets at a lower cost than wet granulation and tableting method, due to a fewer items of process validation. In this study, acetaminophen was used as a medicine with various granular diameters to formulate tablets by direct compression, thus evaluating their physical properties. Consequently, direct compression was found effective in formulating tablets with excellent physical properties, with the granular diameter taken into account. It was confirmed that tablets produced by direct compression were similar in physical properties in tablets produced by wet granulation and tableting method. Further, it was suggested that use of a dry-type binder would make it possible to provide a tablet having higher content of the medicine with excellent physical properties.     

P(VDF-co-TrFE-co-CTFE)-g-SPS共聚物的合成表征

采用商业聚(偏氟乙烯-co-三氟氯乙烯)(P(VDF-co-CTFE)为原料,结合氢化反应、ATRP和磺化反应系统合成了一系列聚(偏氟乙烯-co-三氟乙烯-co-三氟氯乙烯)-g-磺化聚苯乙烯(P(VDF-co-TrFE-co-CTFE)-g-SPS)共聚物.重点研究了测试环境(如温度和相对湿度)、聚合物微观结构(接枝密度,接枝长度等)对聚合物形貌、吸水率和质子传导率的影响.研究表明,在接枝量相同的情况下,随着接枝密度的降低,聚合物的相分离更加明显,亲水相从孤岛型逐渐转变为部分连续型;聚合物的吸水率随磺酸基摩尔含量增加而提高;聚合物的质子传导率随着温度的提高和湿度的降低而降低;在较低温度下,聚合物的电导率随接枝密度的增加而降低,而在较高温度下,聚合物的电导率随接枝密度的增加而升高.组成优化的P(VDF-co-TrFE-co-CTFE)-g-SPS共聚物在30～120℃和高湿度条件下,其质子传导率明显优于Nafion112膜.     

Some physical properties of tabletted seed of Garcinia kola (HECKEL)

The formulation of Garcinia kola seeds into tablet dosage form and evaluation of some physical properties of the tablets are presented. A chemical assay was conducted on the dry, powdered seeds as well as the crude aqueous extract of the seeds. The dry powdered seeds contain 0.003% of flavonoids while the crude extract contained 0.007% of flavonoids based on rutin used as the standard. The powdered material (50 mg) and crude extract (10 mg) were formulated into tablets using the wet granulation method. Named binders were evaluated in these formulations. The various tablet parameters were evaluated, namely: weight variation, thickness and diameter, hardness, friability, disintegration time, dissolution profile and content uniformity. The results indicated that the tablets had good disintegration time, dissolution and hardness/friability profiles. Tablets formulated with starch had the best disintegration properties but were consequently very friable. Tablets formulated from 10 mg of the crude extract needed a larger proportion of diluents, which affected the tablet properties.     

Water adsorption on clay minerals as a function of relative humidity: application of BET and Freundlich adsorption models

Water adsorption on kaolinite, illite, and montmorillonite clays was studied as a function of relative humidity (RH) at room temperature (298 K) using horizontal attenuated total reflectance (HATR) Fourier transform infrared (FTIR) spectroscopy equipped with a flow cell. The water content as a function of RH was modeled using the Brunauer, Emmett, and Teller (BET) and Freundlich adsorption isotherm models to provide complementary multilayer adsorption analysis of water uptake on the clays. A detailed analysis of model fit integrity is reported. From the BET fit to the experimental data, the water content on each of the three clays at monolayer (ML) water coverage was determined and found to agree with previously reported gravimetric data. However, BET analysis failed to adequately describe adsorption phenomena at RH values greater than 80%, 50%, and 70% RH for kaolinite, illite, and montmorillonite clays, respectively. The Freundlich adsorption model was found to fit the data well over the entire range of RH values studied and revealed two distinct water adsorption regimes. Data obtained from the Freundlich model showed that montmorillonite has the highest water adsorption strength and highest adsorption capacity at RH values greater than 19% (i.e., above ML water adsorption) relative to the kaolinite and illite clays. The difference in the observed water adsorption behavior between the three clays was attributed to different water uptake mechanisms based on a distribution of available adsorption sites. It is suggested that different properties drive water adsorption under different adsorption regimes resulting in the broad variability of water uptake mechanisms.     

Fluoroalkyl-functionalized silica particles: synthesis, characterization, and wetting characteristics

Fluoroalkyl-functionalized silica particles for use in nonwetting surfaces were prepared by treatment of silica particles with fluoroalkyl-functional chlorosilanes. Both fumed and precipitated silica were studied, as well as the efficiency of surface coverage using mono-, di-, and trifunctional chlorosilanes. The most effective surface treatment was accomplished via the surface grafting of monofunctional chlorosilanes in the presence of preadsorbed dimethylamine under anhydrous conditions at room temperature. Confirmation of covalent attachment was accomplished via Fourier transform infrared (FT-IR) spectroscopy, while elemental analysis, thermogravimetric analysis, and nitrogen adsorption isotherms were used to determine grafting densities and additional key geometric characteristics of the grafted layer. The effect of residual silanol content on the moisture uptake properties of the modified silica particles was determined by measuring the water uptake of unbound particles, while liquid wetting properties were determined by dynamic contact angle analysis of elastomeric composites. Although residual silanol content was shown to effect wetting properties, results suggest that surface geometry dominates the performance of liquid-repellent surfaces. The potential use of fluoroalkyl-functionalized silica particles for hydrophobic and oleophobic applications is discussed.     

乙酰化对壳聚糖-明胶海绵结构和性能的影响

用乙酸酐对壳聚糖与明胶共混物进行乙酰化,然后冷冻干燥制备乙酰化壳聚糖-明胶海绵,并研究乙酰化对海绵结构与性能的影响。用盐酸环丙沙星作模型药物,探讨载药海绵的抑菌效果。结果表明:制得的海绵具有多孔结构,随壳聚糖在混合物中含量的增加,海绵的吸水率和保水率先增后减;随着乙酰化程度的提高,海绵的吸水率先减后增,而保水率与吸水率的变化规律相反。酶对海绵的降解率不受壳聚糖和明胶混合比例的影响,但随海绵乙酰化程度的增加而增加。载药海绵的抑菌效果与海绵中壳聚糖含量有关。     

磺化聚苯醚酮质子交换膜的制备与表征

设计、合成了一种含氰基双氯单体,其结构特点是氰基分布在3个以间位醚键相连的苯环上。以此单体和2,5-二氯-3'-磺酸钠二苯甲酮为原料,利用Ni(0)催化偶联反应制备了微嵌段型质子交换膜材料(中等长度磺化聚苯-三氰基聚苯醚酮共聚物(m-SPP-co-PAEK 3CN x),x代表聚合物的离子交换容量)。结果表明,与相同离子交换容量的磺化聚合物相比,该类聚合物膜表现出较低的吸水、溶胀率和较低的甲醇渗透性能。以离子交换容量2.16为例,80℃下,m-SPP-co-PAEK 3CN 2.16的吸水率、溶胀率分别为29.7%、28.2%,而SPP-co-PAEK MO 2.33的吸水率、溶胀率分别为80.2%、37.2%。25℃下,二者的甲醇渗透系数分别为2.38和7.20。聚合物骨架结构中存在丰富的氰基基团,导致膜具有良好的尺寸稳定性和较低的甲醇渗透性能。基于这些优异的性能,新制备的膜材料在燃料电池领域显示了潜在的应用前景。