Effects of the Method of Preparation on the Compression,Mechanical, and Release Properties of Khaya Gum Matrices

A study has been made of the compression properties of khaya gum matrices and the effects of drug concentration and method of preparation of the material on the compression, mechanical and the drug release characteristics of the matrices. Khaya gum matrix tablets were prepared by direct compression and wet granulation methods. The compression properties of the formulations were assessed using the equations of Heckel and Kawakita. The mechanical properties of the tablets were evaluated using crushing strength and friability of the tablets, whereas the release properties of the tablets were evaluated by using the disintegration and dissolution times. The results obtained show that khaya gum deformed mainly by plastic deformation. The compression properties of the formulations were affected by the concentration of the drug and the method of preparation of the materials for compression. Tablets prepared by wet granulation showed faster onset and higher amount of plastic deformation during compression than those prepared by direct compression. Tablets containing dicalcium phosphate showed higher mechanical strength and disintegration and dissolution times. Wet granulation also increased the mechanical strength of the tablet without significantly affecting the drug release characteristics from the matrix tablets. Thus, the wet granulation method could be useful in the preparation of khaya gum matrix tablet with acceptable mechanical properties and drug release properties.     

Effects of the method of preparation on the compression, mechanical, and release properties of khaya gum matrices

A study has been made of the compression properties of khaya gum matrices and the effects of drug concentration and method of preparation of the material on the compression, mechanical and the drug release characteristics of the matrices. Khaya gum matrix tablets were prepared by direct compression and wet granulation methods. The compression properties of the formulations were assessed using the equations of Heckel and Kawakita. The mechanical properties of the tablets were evaluated using crushing strength and friability of the tablets, whereas the release properties of the tablets were evaluated by using the disintegration and dissolution times. The results obtained show that khaya gum deformed mainly by plastic deformation. The compression properties of the formulations were affected by the concentration of the drug and the method of preparation of the materials for compression. Tablets prepared by wet granulation showed faster onset and higher amount of plastic deformation during compression than those prepared by direct compression. Tablets containing dicalcium phosphate showed higher mechanical strength and disintegration and dissolution times. Wet granulation also increased the mechanical strength of the tablet without significantly affecting the drug release characteristics from the matrix tablets. Thus, the wet granulation method could be useful in the preparation of khaya gum matrix tablet with acceptable mechanical properties and drug release properties.     

Evaluation of honey locust (Gleditsia triacanthos Linn.) gum as sustaining material in tablet dosage forms

In this study, honey locust gum (HLG) obtained from Gleditsia triacanthos (honey locust) beans was investigated as a hydrophilic matrix material in the tablets prepared at different concentrations (5% and 10%) by wet granulation method. Theophylline was chosen as a model drug. The matrix tablets containing hydroxyethylcellulose and hydroxypropyl methylcellulose as sustaining polymers at the same concentrations were prepared and a commercial sustained release (CSR) tablet containing 200 mg theophylline was examined for comparison of HLG performance. Physical analysis on CSR tablet, matrix tablets and their granules before compression were performed. According to the results obtained from dissolution studies in distilled water, pH 1.2 HCl buffer and pH 7.2 phosphate buffer, no significant difference was found between CSR tablet and the matrix tablet containing 10% HLG in each medium (P > 0.05) and these tablets showed zero-order kinetic model in all the mediums.     

Novel time and site specific “tablets in capsule” system for nocturnal asthma treatment

The objective of present work was to develop a “tablets in capsule” system for facilitating both immediate and pulsatile drug deliveries of theophylline to mimic the circadian rhythm of nocturnal asthma. The system comprised of capsule filled with two tablets, first pulse and second pulse tablet prepared by wet granulation method. First pulse tablet was not coated and was responsible for providing loading dose whereas; second pulse tablet was coated with Eudragit L100 and Eudragit S100 to release drug in colon after specific lag time. Two independent variables, amount of polymers and coating thickness, were optimized by 3² full factorial design. The optimum formulation consisted of Eudragit L100: Eudragit S100 in 1:1.5 ratio and coating thickness of 20 % (w/w). In vitro drug release of “tablets in capsule” system in three different media (pH 1.2, pH 6.8, and pH 7.4) revealed immediate and pulsatile release patterns.     

茶碱缓释片的制备及其初步稳定性考察

目的：考察茶碱羟丙基甲基纤维素（HPMC）骨架片的制备方法及其初步稳定性。方法：以HPMC为骨架材料,采用湿颗粒法制备茶碱缓释片,考察了HPMC用量、HPMC黏度及释放介质pH值对药物体外释放行为的影响,以及光照、高温及高湿度对茶碱缓释片稳定性的影响。结果：HPMC用量和黏度显著影响茶碱释药速率,释放介质pH值对茶碱释药速率影响较小。光照、高温及高湿度不影响茶碱缓释片的含量及释放度。结论：通过使用合适黏度的HPMC及调节HPMC用量可获得具有理想释药行为的茶碱缓释片,且其稳定性良好。     

Compressional characterization of two dextrose-based directly compressible excipients using an instrumented tablet press

The main objective of this work was to evaluate the compaction behavior and record the work and the force involved in the compaction of blends and granules of two dextrose-based directly compressed excipients using a single-punch instrumented tablet press. The second objective was to identify the predominant form of deformation for the two different directly compressible excipients. Anhydrous theophylline (10% w/w) was used as a drug model, Emdex and/or Maltrin M 510 (89.5% w/w) were used as diluent, and magnesium stearate (0.5% w/w) was used as lubricant. All formulations were compressed at four different compressional forces and at a target tablet weight of 450 mg +/- 5%. Results show that compacts prepared from Emdex using the direct compression method produced the lowest elastic work and die wall friction, and the best degree of lubrication. Wet granulation for Maltrin M 510 decreased elastic work, frictional work, and ejection force, and enhanced both net work and degree of lubrication. In general, wet granulation for both Emdex and Maltrin M 510 decreased the crushing strength of the tablets and enhanced the degree of lubrication, compared to direct compression formulations. All formulations showed similar shape pattern for plastic deformation, suggesting that the predominant mechanism of deformation is plastic deformation type a Heckel plots.     

Compressional Characterization of Two Dextrose-Based Directly Compressible Excipients Using an Instrumented Tablet Press

The main objective of this work was to evaluate the compaction behavior and record the work and the force involved in the compaction of blends and granules of two dextrose-based directly compressed excipients using a single-punch instrumented tablet press. The second objective was to identify the predominant form of deformation for the two different directly compressible excipients. Anhydrous theophylline (10% w/w) was used as a drug model, Emdex and/or Maltrin M 510 (89.5% w/w) were used as diluent, and magnesium stearate (0.5% w/w) was used as lubricant. All formulations were compressed at four different compressional forces and at a target tablet weight of 450 mg ± 5%. Results show that compacts prepared from Emdex using the direct compression method produced the lowest elastic work and die wall friction, and the best degree of lubrication. Wet granulation for Maltrin M 510 decreased elastic work, frictional work, and ejection force, and enhanced both net work and degree of lubrication. In general, wet granulation for both Emdex and Maltrin M 510 decreased the crushing strength of the tablets and enhanced the degree of lubrication, compared to direct compression formulations. All formulations showed similar shape pattern for plastic deformation, suggesting that the predominant mechanism of deformation is plastic deformation type a Heckel plots.     

Preparation of Coated Valproic Acid and Sodium Valproate Sustained-release Matrix Tablets

The aim of this research was to investigate the technique for preparation of coated valproic acid and sodium valproate sustained-release matrix tablets. Different diluents were tested and selected as the effective absorbent for oily valproic acid. Effect of the amount of absorbent and hydroxypropylmethylcellulose on drug release from valproic acid-sodium valproate matrix tablets prepared with wet granulation technique was evaluated in pH change system. Colloidal silicon dioxide effectively adsorbed liquid valproic acid during wet granulation and granule preparation. The amounts of colloidal silicon dioxide and hydroxypropylmethylcellulose employed in tablet formulations affected drug release from the tablets. The drug release was prominently sustained for over 12 h using hydroxypropylmethylcellulose-based hydrophilic matrix system. The mechanism of drug release through the matrix polymer was a diffusion control. The drug release profile of the developed matrix tablet was similar to Depakine Chrono^®, providing the values of similarity factor (f2) and difference factor (f1) of 85.56 and 2.37, respectively. Eudragit^® L 30 D-55 was used as effective subcoating material for core matrix tablets before over coating with hydroxypropylmethylcellulose film with organic base solvent. Drug release profile of coated matrix tablet was almost similar to that of Depakine Chrono^®.     

Sustained release of acetaminophen from a heterogeneous mixture of two hydrophilic non-ionic cellulose ether polymers

This study examined the release of acetaminophen (APAP) from hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC) matrices. The effect of pseudoephedrine (PE) as a co-active, HPMC:HPC ratio, polymer loading, pH of the dissolution media, and compression force on APAP release were studied. Granules formulated with APAP or both APAP and PE, and various blends of HPMC and HPC were compressed into tablets at different compression forces. APAP release from the matrix tablets was not considerably influenced by changes in HPMC:HPC ratio or compression force. The rate of drug release was significantly affected by pH of the dissolution media, total polymer loading, and the presence of PE. Drug release from the formulations containing both APAP and PE was slower than those containing only APAP. Drug release from tablets formulated with APAP only showed an initial burst at pH 1.16 or 7.45. Formulations containing both APAP and PE showed slower drug release at pH 1.16 than at pH 7.4. The drug release data showed a good fit to the Power Law Model. The mechanism of drug release is consistent with a complex behavior. The results of the tablet erosion studies indicated that the amount of APAP released was linearly related to the percentage of tablet weight loss. The kinetics of tablet water uptake was consistent with a diffusion and stress relaxation mechanism.     

复方缬沙坦/苯磺酸氨氯地平片的制备和体外溶出测定

目的:研制与上市品具有相似体外溶出的复方缬沙坦/苯磺酸氨氯地平片。方法:采用湿法制粒压片工艺制备自制品,通过单因素试验初步筛选处方,中心复合设计优化处方。比较不同pH溶出介质(pH 1.2盐酸、pH 4.5乙酸缓冲液和0.1%聚山梨酯80-pH 6.8磷酸缓冲液)中自制品与市售复方片的溶出行为,通过相似因子f2计算,评价2种药物体外溶出的相似性。结果:与市售片比较,以优化处方制备的复方片中缬沙坦和苯磺酸氨氯地平在不同pH值溶出介质中的溶出度相似因子f 2均>50。结论:自制的复方片与市售片体外溶出行为相似。     

Tablet formulation studies on an oxcarbazepine-beta cyclodextrin binary system

Oxcarbazepine is a poorly water-soluble (0.083 mg/ml) anti-epileptic drug according to the BCS system (class II) and its dissolution is rate-limiting step for its absorption. The objective of this work was to develop tablet formulations of oxcarbazepine-beta-cyclodextrin (OX-beta-CD) binary systems. Three types of binary systems--physical mixtures, kneaded systems, and coevaporated systems--were studied. Phase solubility studies indicated 1:1 M complexation of oxcarbazepine with beta-cyclodextrin. Drug-beta-CD binary systems were prepared at 1:1 molar ratios and used in formulation studies. The dissolution properties of OX-beta-CD KS (kneaded system, 100.10% drug release in 15 min) were superior than those of the other binary system and pure oxcarbazepine. The tablet formulations containing drug-beta-CD binary systems prepared by wet granulation and direct compression showed superior dissolution properties when compared with the formulations of the corresponding pure drug formulations. Tablet formulations containing drug-beta-CD binary systems prepared by the kneading method showed good dissolution properties (100% drug release in 15 min in direct compression method and 99.9% drug release in 20 min in wet granulation method). Overall, the dissolution properties of tablet formulations prepared by the direct compression method were superior to those of tablets prepared by the wet granulation method. Accelerated stability studies on some selected tablet formulations were also conducted by keeping the samples at 40 +/- 2 degrees C and 75% relative humidity. There were no statistical differences in the percentage of drug dissolved at 15 and 20 min between fresh and stored samples at the different time points (P < 0.05). Drug content also remained within acceptable limits. Thus, drug-beta-CD binary systems are useful in developing tablet formulations of oxcarbazepine with improved dissolution properties.     

Development and evaluation of natural gum-based extended release matrix tablets of two model drugs of different water solubilities by direct compression

The study was aimed at developing extended release matrix tablets of poorly water-soluble diclofenac sodium and highly water-soluble metformin hydrochloride by direct compression using cashew gum, xanthan gum and hydroxypropylmethylcellulose (HPMC) as release retardants. The suitability of light grade cashew gum as a direct compression excipient was studied using the SeDeM Diagram Expert System. Thirteen tablet formulations of diclofenac sodium (∼100 mg) and metformin hydrochloride (∼200 mg) were prepared with varying amounts of cashew gum, xanthan gum and HPMC by direct compression. The flow properties of blended powders and the uniformity of weight, crushing strength, friability, swelling index and drug content of compressed tablets were determined. In vitro drug release studies of the matrix tablets were conducted in phosphate buffer (diclofenac: pH 7.4; metformin: pH 6.8) and the kinetics of drug release was determined by fitting the release data to five kinetic models. Cashew gum was found to be suitable for direct compression, having a good compressibility index (ICG) value of 5.173. The diclofenac and metformin matrix tablets produced generally possessed fairly good physical properties. Tablet swelling and drug release in aqueous medium were dependent on the type and amount of release retarding polymer and the solubility of drug used. Extended release of diclofenac (∼24 h) and metformin (∼8–12 h) from the matrix tablets in aqueous medium was achieved using various blends of the polymers. Drug release from diclofenac tablets fitted zero order, first order or Higuchi model while release from metformin tablets followed Higuchi or Hixson-Crowell model. The mechanism of release of the two drugs was mostly through Fickian diffusion and anomalous non-Fickian diffusion. The study has demonstrated the potential of blended hydrophilic polymers in the design and optimization of extended release matrix tablets for soluble and poorly soluble drugs by direct compression.     

黄原胶亲水性骨架片体外释药的影响因素

以茶碱为模型药物,制备了黄原胶亲水性骨架片,研究了体外释药的影响因素．结果表明,茶碱黄原胶亲水性骨架片的释药速率与骨架片中黄原胶的用量和溶出条件（ 转速、介质离子强度、ｐＨ 值） 有关,但与制备工艺条件无关．溶出介质中离子对其释药机制有影响．黄原胶能有效控制骨架片中药物释放,是一种优良的亲水性骨架材料．     

Process to manufacture effervescent tablets: air forced oven melt granulation

In the present study we apply melt granulation in an air forced oven, called "are forced oven melt granulation" to the single-stage manufacture of effervescent granules consisting of anhydrous citric acid (43.2%) and sodium bicarbonate (56.8%) in order to make tablets. This study established that process parameters such as concentration of PEG 6000, residence time in the air forced oven, fineness of PEG 6000, fineness of the initial effervescent mix and efficiency of two lubricants markedly influenced several granule and tablet characteristics. The granules ready to be compressed into tablets were stable for 7 days at 60% RH/18 degrees C. It is a dry, simple, rapid, effective, economical, reproducible process particularly well suited to the manufacture of effervescent granules which are easily compressed into effervescent tablets. Of all the formulations tested, only formulations B2 and E2 melt granulated for 30 minutes gave tablets which had optimum compression characteristics without processing problems during compression.     

无时滞非达霉素肠溶片的制备及溶出评价

目的: 制备无时滞非达霉素肠溶片,考察其溶出特性。方法: 采用湿法制粒工艺,通过正交实验进行片芯优化,以甲基丙烯酸与丙烯酸乙酯共聚物为肠溶包衣材料,制备非达霉素肠溶片,以体外释放度为指标,考察其溶出行为。结果: 片芯中羟丙甲纤维素和交联羧甲基纤维素钠的用量分别为1.2%和4.5%,微晶纤维素和淀粉的比例为3:1,肠溶层共聚物的比例为50%时,制备的非达霉素肠溶片在pH1.0盐酸中2h释放度小于10%,在pH4.5醋酸盐缓冲液中可以崩解释放,在pH6.8磷酸盐缓冲液中快速释放,10min释放度大于60%。结论: 制备的非达霉素肠溶片与普通肠溶片相比无时滞效应,有望进行工业化生产。     

Design and evaluation of a controlled-release theophylline tablet. Preliminary communication

A 300 mg controlled-release theophylline formulation was developed as a tablet prepared by wet granulation using the acrylic resins Eudragit S 100R and Eudragit RSPMR. The tablet was compared with a marketed controlled-release capsule using in vivo and in vitro tests. The in vitro dissolution of theophylline from the tablets followed an apparent zero order kinetics. The in vivo comparison was performed in a cross over fashion in four healthy volunteers who received one tablet or capsule every 12 hours during seven days. The results showed no statistically significant differences in AUC, tmax and in plasma theophylline concentrations at the different times. Nevertheless, concentrations were lower after the administration of the tablets than when the volunteers received the capsules. On the other hand, the apparent elimination half lives obtained after the tablets were longer than with the capsules. An excessive retardation in the release of theophylline from the tablet could be responsible for this fact.     

Evaluation of the gum from Hakea gibbosa as a sustained-release and mucoadhesive component in buccal tablets.

The objective of this paper was to evaluate the mucoadhesive and sustained-release properties of the water-soluble gum obtained from Hakea gibbosa (hakea), for the formulation of buccal tablets. Flatfaced tablets containing hakea were formulated using chlorpheniramine maleate (CPM) as a model drug. Two types of tablets were prepared: uncoated tablets (type I) and tablets in which all but one face of the type I tablet was coated with hydrogenated castor oil (Cutina) using a compression coating technique (type II). In an attempt to explain the observed sustained-release effect, the potential for a chemical interaction between hakea and CPM was evaluated by FTIR, differential scanning calorimetry (DSC), UV spectroscopy, and acid-base titrations. Mathematical modeling of the CPM release data was developed to elucidate the mechanism of drug release. The mucoadhesive strength was evaluated by quantitating the force of detachment. Finally, the rates of water uptake and erosion were determined for the buccal tablets. The time required for 90% of the CPM to be released in vitro (t90%) was used as a basis for comparison. For formulations that did not contain hakea, the t90% was 14 min for both directly compressed and wet granulated tablets, whereas the t90% for wet granulated tablets containing 2 or 32 mg hakea/tablet was 36 and 165 min, respectively. Directly compressed tablets containing 2, 12, 22, and 32 mg hakea/tablet displayed t90% values of 48, 120, 330, and 405 min, respectively. DSC, FTIR, UV spectroscopy and acid-base titration experiments suggested the absence of chemical interactions. The force of detachment for directly compressed and wet granulated tablets increased from 0.70 +/- 0.3 to 4.08 +/- 0.52 N and from 0.65 +/- 0.28 to 3.94 +/- 0.31 N as the amount of hakea per tablet was increased from 0 to 32 mg, respectively, at a 5 N attachment compression force. The novel natural gum, hakea, may not only be utilized to sustain the release of CPM from a unidirectional-release buccal tablet, but it also exhibited excellent mucoadhesive properties. The mechanism by which CPM release was sustained was more likely due to slow relaxation of the hydrated hakea. The mucoadhesive strength can be modulated by altering the amount of hakea in the tablet.     

Development of oral controlled-release tablet formulations based on diltiazem-carrageenan complex

Diltiazem HCl and lambda carrageenan react in distilled water to give a slightly soluble interaction product. The aim of this work was to verify the possible employment of lambda carrageenan-diltiazem (DTZ) complex in controlled-release formulations. The influence of complex particle size, compression force, pH of the dissolution medium, and tablet dimensions on drug release has been evaluated. The results confirm the suitability of the DTZ-carrageenan interaction product for controlled-release formulations. Good compaction properties allow tablets to slowly erode, with only the addition of the amount of hydroxypropyl methylcellulose (HPMC) necessary as a binding agent. The use of the finest sieve fraction results in the highest crushing strength values and in the slowest release rate, both in pH 1.2 and in pH 6.8. The force of compression does not affect the drug release for values over 16 kN. The release rate increases when the geometry of the tablet is varied so the surface/ volume ratio of the tablet is increased, suggesting a release mechanism involving surface dissolution/erosion.     

In vitro dissolution kinetic study of theophylline from hydrophilic and hydrophobic matrices

Oral dosage forms containing 300 mg theophylline in matrix type tablets, were prepared by direct compression method using two kinds of matrices, glycerylbehenate (hydrophobic), and (hydroxypropyl)methyl cellulose (hydrophilic). The in vitro release kinetics of these formulations were studied at pH 6.8 using the USP dissolution apparatus with the paddle assemble. The kinetics of the dissolution process were studied by analyzing the dissolution data using four kinetic equations, the zero-order equation, the first-order equation, the Higuchi square root equation and the Hixson-Crowell cube root law. The analysis of the dissolution kinetic data for the theophylline preparations in this study shows that it follows the first order kinetics and the release process involves erosion / diffusion and an alteration in the surface area and diameter of the matrix system, as well as in the diffusion path length from the matrix drug load during the dissolution process. This relation is best described by the use of both the first-order equation and the Hixson-Crowell cube root law.     

Interaction of omapatrilat with FD&C Blue No. 2 lake during dissolution of modified release tablets

The purpose of this study was to identify the mechanism(s) of omapatrilat degradation observed during dissolution from modified release (MR) tablet formulations containing colorants. The tablets were manufactured by a dry granulation process employing roller compaction. The colorants were added intragranularly and included red and yellow iron oxides and FD&C Blue No. 2 lake and dye. Dissolution studies in pH 6 or 6.8 media do not indicate any omapatrilat degradation in the absence of colorants. In the presence of colorants the degradation rate of omapatrilat in pH 6.8 media was in the following order: blue lake>blue lake+yellow iron oxide>yellow and red iron oxides. Higher degradation was observed with MR tablets formulated with indigo carmine (dye) as opposed to tablets formulated with aluminum oxide or aluminum hydroxide (dye substrate portion of lake). The inclusion of tartaric acid and the photostabilizer, uric acid, in omapatrilat MR tablets containing the blue lake reduced the degradation significantly. The dissolution instability observed at pH 6.8 in the MR tablet formulated with FD&C Blue No. 2 Lake was attributed to the dye component of the lake. The instability was more pronounced at higher pH and in the absence of a photostabilizer.