Properties of lipophilic matrix tablets containing phenylpropanolamine hydrochloride prepared by hot-melt extrusion.

The objective of the present study was to investigate the influence of formulation factors on the physical properties of hot-melt extruded granules and compressed tablets containing wax as a thermal binder/retarding agent, and to compare the properties of granules and tablets with those prepared by a high-shear melt granulation (MG) method. Powder blends containing phenylpropanolamine hydrochloride, Precirol and various excipients were extruded in a single-screw extruder at open-end discharge conditions. The extrudates were then passed through a 14-mesh screen to form granules. The extrusion conditions and the optimum amount of wax to function as the thermal binder were dependent on the properties of the filler excipients. At the same wax level, drug release from tablets decreased in the order of using microcrystalline cellulose (MCC), lactose and Emcompress as the filler excipient. The observed differences in the dissolution properties of the tablets were due to the differences in the solubility, swellability and density of the filler excipients. Replacing Precirol with Sterotex K, a higher melting point wax, resulted in slightly increased dissolution rates, when the extrusion was performed at the same temperature conditions. Hot-melt extruded granules were observed to be less spherical than high-shear melt granules and showed lower values of bulk/tap densities. However, tablets containing MCC or lactose granules prepared by hot-melt extrusion (HME) exhibited higher hardness values. Slower drug release rates were found for tablets containing MCC by HME compared with MG. Analysis of the hot-melt extruded granules showed better drug content uniformity among granules of different size ranges compared with high-shear melt granules, resulting in a more reproducible drug release from the corresponding tablets.     

Influence of thermal processing on the properties of chlorpheniramine maleate tablets containing an acrylic polymer

The purpose of this investigation was to determine the effects of thermal processing and post-processing thermal treatment on the release properties of chlorpheniramine maleate (CPM) from matrix tablets containing Eudragit RS PO and triethyl citrate (TEC). CPM tablets containing Eudragit RS PO with and without TEC were prepared by direct compression (DC), high shear hot-melt granulation (HMG), and hot-melt extrusion (HME). X-ray diffraction patterns showed that the CPM was distributed in Eudragit RS PO at the molecular level following HME. The thermogravimetry analysis (TGA) profiles of CPM, Eudragit RS PO, and TEC demonstrated that these materials were thermally stable during both the high shear HMG and HME processes. The tablets were subjected to post-processing thermal treatment by storing the tablets at 60 degrees C in open containers for 24 hr. Tablets prepared by DC showed the highest drug release rate constant of 36.2% hr-1/2. When 4% TEC was incorporated into the formulation, the drug release rate constant for the directly compressed tablets decreased to 32.4% hr-1/2. After high shear HMG and HME of the powder blend containing 4% TEC, the drug release rate constant decreased to 30.8 and 13.8% hr-1/2 for the respective processes. The drug release rate constants for all tablets decreased following post-processing thermal treatment. The reduction in release rate was due to an increase in the intermolecular binding and entanglement between drug molecules and polymer molecules that occurred during thermal processing. Post-processing thermal treatment of the hot-melt extrudates had a minimal effect on the drug release rate since the HME process enhanced the drug and polymer entanglement to a greater extent.     

Properties of sustained-release tablets prepared by hot-melt extrusion

The objectives of the present study were to investigate the properties of polyethylene oxide (PEO) as a drug carrier and to study the release mechanism of chlorpheniramine maleate (CPM) from matrix tablets prepared by hot-melt extrusion. During the hot-melt extrusion process, a dry powder blend of drug, polymer, and other adjuvants was fed into the extruder and melted inside the barrel of the machine. The molten mass was extruded through a rod-shaped die and then cut manually into 400-mg tablets. CPM and PEO were shown to be stable under the processing conditions. The molecular weight of the PEO, the drug loading percentage, and the inclusion of polyethylene glycol as a processing aid, were all found to influence the processing conditions and the drug release properties of the extruded tablets. Faster release of CPM from the matrix tablets was observed in acidic medium than in purified water and phosphate buffer (pH 7.4). Drug release from the matrix tablet was controlled by erosion of the PEO matrix and the diffusion of the drug through the swollen gel layer at the surface of the tablets. CPM was dispersed at the molecular level in the PEO matrix at low drug loading level and recrystallization of CPM was observed at high drug loading levels. Hot-melt extrusion was demonstrated to be a viable novel method to prepare sustained-release tablets. PEO was shown to be a suitable polymeric carrier for this process.     

Use of factorial design to evaluate granulations prepared by spheronization.

This study was designed to demonstrate that properties of a granulation with a given composition, prepared by the spheronizing technique, could be altered by slight changes in process variables alone to satisfy the requirements of the formulator. A complete factorial experimental design was found satisfactory for demonstrating the range of properties to be expected and for showing statistically significant main effects and any linear interactions between selected variables. Results using two levels of five variables showed that initial water content and spheronizer speed had significant main effects on all primary granulation properties studied. While only one formulation was studied, the data suggest that the factorial design can have utility in predicting the properties of granulations prepared at conditions within the limits imposed by the equipment or formulation.     

反相高效液相色谱法测定布洛芬片的含量

目的建立布洛芬片中布洛芬含量的HPLC测定法。方法采用十八烷基硅烷键合硅胶柱,流动相:醋酸钠缓冲液(取醋酸钠6.13 g,加水750 m l,振摇使溶解,用冰醋酸调节pH值至2.5)-乙腈(40∶60),流速为1.0 m l.m in-1,检测波长为263 nm。结果线性范围:10.22~102.2 mg.L-1(r=0.99999)。精密度:RSD为0.18%(n=5)平均回收率为99.5%。结论试验表明,该方法简便,快速,结果准确,重现性     

Comparison of the antinociception produced by two oral formulations of ibuprofen: ibuprofen effervescent vs ibuprofen tablets

Objective: The aim of this study was to compare the dose-related effects of both ibuprofen tablets and ibuprofen effervescent [placebo, 400 and 800 mg ibuprofen (Aktren)] on phasic pain. Patients: Twenty volunteers participated in this randomized, double-dummy, fivefold crossover study. Methods: Measurements were obtained before and 15, 60 and 240 min after drug administration. Pain was produced by CO₂ pulses applied to the left nostril. Subjects rated the intensity of the painful stimuli by means of a visual analogue scale. In addition, chemosomatosensory event-related potentials were recorded. Results: In line with previous work, ibuprofen produced a dose-related decrease in pain-related potential amplitudes P1N1, indicating its antinociceptive effects. Higher plasma concentrations of ibuprofen were reached 15–40 min after administration of the effervescent while ibuprofen tablets had a t_max 60–90 min after administration. In addition, 60 min after intake of the effervescent a prolongation of the latencies of the potentials was observed, possibly reflecting superior antinociceptive properties when compared to ibuprofen tablets. In addition, the effervescent appeared to have more consistent effects on intensity estimates compared to ibuprofen tablets. Received: 13 June 1996 / Accepted in revised form: 22 November 1996     

Improvement by super disintegrants of the properties of tablets containing lactose,prepared by wet granulation

International Journal of Clinical Pharmacy - The crushing strength, disintegration and dissolution properties of tablets, made by wet granulation with lactose as filler, gelatin as binder, potato...     

Determination of ibuprofen and naproxen in tablets

Ibuprofen and naproxen have been quantified in tablets by capillary isotachophoresis. Hydrochloric acid (10 mmol/l) adjusted with creatinine to pH 5.0 plus 0.1% polyvinylpyrrolidone was used as the leading electrolyte and 10 mmol/l 4-morpholineethanesulfonic acid as the terminating electrolyte. Linearity was observed from 40.0 to 200.0 mg/l of ibuprofen (naproxen), with a coefficient of determination (r²) of 0.999. Good quantitation was obtained in short analysis time. The isotachophoretic results were compared with those obtained by the fluorescence spectrometry. Experimental parameters for ibuprofen were: λ_EX=224 nm and λ_EM=290 nm. Experimental parameters for naproxen were: λ_EX=230 nm and λ_EM=355 nm. The calibration plot was found to be linear in the range 0.4–2.4 mg/l for ibuprofen and 5.0–20.0 μg/l for naproxen. The minimal sample pretreatment and relatively low running cost make isotachophoresis a good alternative to existing methods.     

用HPLC法测定布洛芬片的含量

布洛芬片是临床常用的一种非甾体类消炎镇痛药，主要用于风湿及类风湿性关节炎的治疗。《中华人民共和国药典》2005年版二部采用酸碱滴定法测定布洛芬含量，此方法是将称取的供试品先溶解再滤过，并洗涤多次，操作繁琐、费时，而且有可能因转移不完全而导致结果出现偏差。本研究参考《国家药品标准》新药转正标准（第30册，178页）的方法，改用HPLC法，改进流动相，建立了一种简便、有效地测定布洛芬含量的方法。     

Comparative human study of ibuprofen enantiomer plasma concentrations produced by two commercially available ibuprofen tablets

Twelve healthy male subjects participated in a two-way Latin square crossover study in which the treatments were a single 400 mg generic ibuprofen tablet (Tablet A) or a single 400 mg MOTRIN Tablet (Tablet B). Blood samples were drawn at various times through 12 h after dosing and plasma samples were assayed for ibuprofen enantiomers with a stereospecific capillary gas chromatographic procedure. Concentration-time data for both enantiomers were in agreement and indicated that drug was absorbed much more quickly from Tablet B than from the Tablet A; enantiomer Tmax values were less than 1.3 h from Tablet B but longer than 4 h from the Tablet A (p less than 0.001). Also, maximum enantiomer plasma concentrations from the Tablet B were about 50 per cent of the peak concentrations observed from Tablet A (p less than 0.001). The total extent of drug absorption appeared to be the same in both products. These data clearly indicate that the two tablets are not bioequivalent with respect to either ibuprofen enantiomer.     

Plasticization and antiplasticization of an acrylic pressure sensitive adhesive by ibuprofen and their effect on the adhesion properties

In transdermal patches, an unpredictable alteration of the mechanical behavior of the pressure sensitive adhesive (PSA) can occur if a drug is added. In the present study, the suitability of Dynamic Mechanical Analysis (DMA)/Dynamic Mechanical Thermal Analysis (DMTA) as methodologies to detect the change in adhesion properties caused by the addition of an API was examined. With DMA/DMTA, time- and temperature-dependent viscoelastic properties were determined. Tack and shear adhesion of blends of the acrylic adhesive DuroTak® 87-4287 and ibuprofen at increasing concentrations were investigated. Interestingly, the probe tack test showed highest values at 1% ibuprofen concentration in the PSA and decreasing values with increasing ibuprofen concentrations. The shear adhesion of the PSA was decreased at all investigated ibuprofen concentrations. With DMA/DMTA, it could be demonstrated that antiplasticization and plasticization are responsible for the change in tack. The main reason for the decrease in shear adhesion is a shift of the T_g to lower temperatures, while antiplasticization only has a marginal effect. The term “antiplasticizing space” was introduced because antiplasticization depends on time, temperature, stress, strain, and API concentration. In general, this antiplasticizing space can have an impact on processing, stability, and in vivo behavior of API/polymer blends in drug formulations.     

Inulin as filler-binder for tablets prepared by direct compaction.

The tabletting properties of a number of different amorphous inulin types were investigated. The types varied with respect to chain length, particle size and amount of included air in the particles. Powder flow properties and densities of the different types were investigated. Just as expected, it was found that the flow properties improved with increased particle size of the material. Compactibility was investigated by compression of tablets on a compaction simulator, simulating the compression on high-speed tabletting machines. The bonding capacity of all inulins was high. However, the lubricant sensitivity strongly varied among the different types of inulin. Generally, amorphous materials such as starches are highly lubricant sensitive, because they show ductile behaviour upon compaction. On the other hand, crystalline materials such as dicalcium phosphate dihydrate have a low lubricant sensitivity, because they fragment during compaction. A high lubricant sensitivity was indeed found for amorphous inulins with a low amount of entrapped air. In contrast, the lubricant sensitivity of the amorphous inulin was low when particles containing large amounts of air were compressed. Obviously entrapped air induces fragmentation of the powder particles by which the lubricant film, covering the particles, was destroyed. Tablets prepared from inulin did not disintegrate but they dissolved when incubated in water. The disintegration/dissolution time increased with decreasing chain length of the inulin. The addition of a disintegrant reduced the disintegration time. The somewhat slower dissolution of the longer chain inulin can be an advantage for chewable tablets or lozenges. It was concluded that inulin with large amounts of entrapped air is a good filler-binder and an attractive alternative to commonly used filler-binders.     

单剂量口服布洛芬控释片的药物动力学与相对生物利用度

研究单剂量ｐｏ布洛芬控释片与缓释胶囊后，血清中的药物动力学与相对生物利用度。结论两种制剂单剂量给药６００ｍｇ时为生物等效；以Ｂ为标准参比制剂，单剂量给药时Ａ相对生物利用度为     

Design and study of ibuprofen disintegrating sustained-release tablets comprising coated pellets.

One challenge in tableting of sustained-release multiparticulates is maintaining the desired drug release after compaction. The aim of this study was to design sustained-release ibuprofen tablets which upon oral ingestion rapidly disintegrate into sustained-release pellets in which the integrity of the pellet core and/or coat is preserved. First free films composed of Eudragit RS 30D and RL 30D in 4:1 ratio and containing different levels of triethyl citrate (TEC) were prepared and tested to optimize the plasticizer level. Cured Eudragit based pellets with 60% ibuprofen loading which in our previous study showed proper mechanical properties for compression were coated with Eudragit RS 30D/RL 30D (4:1) containing 20% triethyl citrate at different coating levels. The mechanical properties of the coated pellets were tested. Polymer coated pellets were compacted into tablets either alone or with a blend of excipients comprising Avicel, PEG 4000, cross-linked PVP. A 3(2) full factorial design was used to optimize the filler blend composition. Effects of pellet to filler ratio, compression force and granulation of filler on tablet characteristics were investigated. Results of mechanical test showed that the coating of cured pellets had no significant effect on yield point and elastic modulus of the pellets. In the case of 5% coating level sustained release of ibuprofen over a period of 24h was achieved. The results obtained from tableting procedure showed that by selecting suitable filler blend (60% Avicel, 10% cross-linked PVP and 30% PEG 4000), compression force, and granulation of filler it was possible to prepare sustained-release tablets containing high ratio of coated pellets (even 80%) with desirable strength, disintegration time, and drug release rate. It was observed that compression force, pellet to filler ratio, composition of filler blend and granulation of fillers had no effect on drug release rate from compacted pellets but had significant influence on tablet strength, friability, and disintegration time. SEM graphs and in vitro release profiles for compacted pellets showed no apparent damage to the coated pellets as a result of the compaction process.     

Clinical pharmacology of predisintegrated ibuprofen 800 mg tablets: an endoscopic and pharmacokinetic study

Thirty-five healthy adults were randomized to receive either: (1) ibuprofen 800 mg tablets; (2) ibuprofen 800 mg aqueous suspension; (3) ibuprofen 800 mg orange juice suspension; or (3) 325 mg aspirin tablets. All treatments were tid for 7 days. Pharmacokinetic sampling was conducted on days 1, 4 and 8. Gastroduodenoscopy was performed on days 1 and 8. Side effects and safety laboratory tests were monitored throughout the study. On day 8 the aspirin group showed significantly more gastric irritation than all of the ibuprofen groups (P less than .005). Both ibuprofen suspension groups showed more gastric irritation than the ibuprofen tablet group (P less than .1). The duodenal scores did not differ among the treatment groups. The aspirin group experienced a higher rate of tinnitus and abdominal pain. The rate and extent of absorption of the ibuprofen suspensions were significantly less than that of the tablets. These data suggest that the taking of ibuprofen as an extemporaneous suspension is therapeutically inferior to ibuprofen tablets and therefore should be discouraged.