An approach to controlled-release dosage form of propranolol hydrochloride

It is possible to release a drug with only limited diffusion from a membrane-coated system using osmotic pumping. In this study, a propranolol osmotic pump was produced by coating the core tablets with cellulose acetate. The effects of membrane thickness, pore size, and stirring rate on the release rate of propranolol hydrochloride were studied. It was found that the thickness of cellulose acetate membrane had a profound effect on the release rate of propranolol hydrochloride from the membrane-coated tablets. The results showed that, when the membrane thickness increased, the release rate of propranolol decreased. The drug release follows a zero-order release when the delivery orifice is between 200 and 800 μm, but when the delivery orifice size is increased to 1000μm, the release kinetic is abnormal. Fluid dynamics have an important effect on the delivery rate of propranolol from this device; the delivery rate increases as a function of the fluid flow. The drug release is higher under a turbulent condition with high rate of stirring.     

New controlled-release ibuprofen tablets

Tablets containing two different doses of ibuprofen are realized. The first possesses very fast release kinetics, while the second has slow and linear release kinetics. This allows drug to produce a therapeutic effect quickly and to maintain it for a long time with only one administration unit. Such tablets are obtained by compression of a mixture of two very different kinds of granulates: an ibuprofen-starch granulate and an ibuprofen-Eudragit RS microsphere granulate. Specific proportions of mixtures of them give the described result after compression at particular tablet hardnesses.     

Dissolution properties of direcet compression tablets containing an agglomerated cellulose powder

In previous studies a novel agglomerated cellulose powder was shown to own advantageous properties for direct compression. Due to the favourable particle and powder properties this material has good binding and disintegration ability in direct compression tablets. In this study the dissolution properties of direct compression tablets containing the agglomerated cellulose powder as a fillerbinder were evaluated. Especially the effect of the amount of cellulose, the porosity of tablets, the solubility of drug material and the amount and the amount and mixing method of lubricant, magnesium stearate were studied.

Tablets containing different amounts of cellulose with dicalcium phosphate as a filler and 10 wt % of water soluble sodium tolmetin as a drug were compressed at a constant pressure of 150 MPa. The breaking strength of tablets increased with increasing amounts of agglomerated cellulose powder. However, the dissolution of drug accelerated up to cellulose amount of 50 wt %. This was due to the ability of the agglomerated cellulose powder to enhance the water penetration into powder compact and the loosening of tablet structure, i.e. formation of cracks.

Tablets containing 20 wt % of cellulose material and 10 wt % of drug material were compressed to different porosities. Tablet porosity had no effect on dissolution of poorly water soluble tolfenamic acid. Also the dissolution of water soluble sodium tolmetin was only slightly affected by the porosity of tablets. This supports the suggested disintegrant mechanism of the agglomerated cellulose powder. The expansion of cellulose agglomerates, which have been deformed, under compression, is widely responsible for the disintegration of the tablets. An increase in the amount as well as in the mixing intensity of magncsium stearate decreased the dissolution of sodium tolmetin from tablets containing 20 wt % of agglomerated cellulose. However, the intrinsic wetting and dissolution phenomens were practically unchanged when the amount of magnesium stearate was below 2 wt %. Thus, the retardation of drug dissolution was acceptable at low lubricant concentrations.

The properties of tablets containing the agglomerated cellulose were compared to those containing microcrystalline cellulose. In all cases tablets containing the agglomerated cellulose powder liberated drug clearly faster and more properly than corresponding microcrystalline cellulose tablets.     

Blinding controlled-release tablets for clinical trials

The objective of the current study was to develop a method to blind commercially available Wellbutrin® SR 150 mg sustained-release tablets for a clinical study. Overcoating was selected as the most appropriate blinding method. Hydroxypropyl methylcellulose (Opadry® II) containing red iron oxide and titanium dioxide was applied to the Wellbutrin tablets at coating levels ranging from 0.5% to 4% weight gain. When compared against the uncoated product, no significant differences in drug release were noted over an 8-hr period. Matching placebo tablets, prepared using specially designed tablet tooling, were coated with the same cellulosic polymer that was used for the active. The coated active and placebo tablets were virtually indistinguishable. To test the applicability of this overcoating technique for blinding other controlled release products, the same procedure was used to coat Glucotrol® XL 5 mg tablets and Theo-Dur 200 mg tablets. The debossing on the Theo-Dur tablets and the laser-drilled hole on the surface of the Glucotrol tablets prevented blinding. The Theo-Dur tablets were mechanically weak and not able to withstand the coating process. Dissolution testing revealed significantly higher amounts of drug were released from the blinded Glucotrol tablets compared to the unblinded product at the 12 hr time point. The findings from this study suggest that overcoating with pigmented hydroxypropyl methylcellulose may not be useful for blinding all controlled-release tablets.     

Formulation, in-vitro release and therapeutic effect of hydrogels based controlled release tablets of propranolol hydrochloride

Matrix based controlled release tablets of Propranolol Hydrochloride (PHCL) were formulated using hydroxy propyl methyl cellulose (HPMC), sodium carboxy methyl cellulose (sod. CMC) and their combinations. The in-vitro dissolution kinetics revealed a zero order release for selected drug, HPMC and sod. CMC combination. The selected formulation was evaluated in mongrel dog by recording the isoprenaline induced tachycardia and measuring the inhibition of tachycardia. The results showed the sustaining therapeutic effect of the formulation.     

Formulation,in-vitro release and therapeutic effect of hydrogels based controlled release tablets of propranolol hydrochloride

Abstract

Matrix based controlled release tablets of Propranolol Hydrochloride (PHCL) were formulated using hydroxy propyl methyl cellulose (HPMC), sodium carboxy methyl cellulose (sod. CMC) and their combinations. The in-vitro dissolution kinetics revealed a zero order release for selected drug, HPMC and sod. CMC combination. The selected formulation was evaluated in mongrel dog by recording the isoprenaline induced tachycardia and measuring the inhibition of tachycardia. The results showed the sustaining therapeutic effect of the formulation.     

Development of orally disintegrating tablets comprising controlled-release multiparticulate beads

Melperone is an atypical antipsychotic agent that has shown a wide spectrum of neuroleptic properties, particularly effective in the treatment of senile dementia and Parkinson’s-associated psychosis, and is marketed in Europe as an immediate-release (IR) tablet and syrup. An orally disintegrating tablet (ODT) dosage form would be advantageous for patients who experience difficulty in swallowing large tablets or capsules or those who experience dysphagia. Controlled-release (CR) capsule and ODT formulations containing melperone HCl were developed with target in vitro release profiles suitable for a once-daily dosing regimen. Both dosage forms allow for the convenient production of dose-proportional multiple strengths. Two ODT formulations exhibiting fast and medium release profiles and one medium release profile capsule formulation (each 50?mg) were tested in vivo using IR syrup as the reference. The two medium release formulations were shown to be bioequivalent to each other and are suitable for once-daily dosing. Based on the analytical and organoleptic test results, as well as the blend uniformity and in-process compression data at various compression forces using coated beads produced at one-tenth (1/10) commercial scale, both formulations in the form of CR capsules and CR ODTs have shown suitability for progression into further clinical development.     

Dissolution test for silymarin tablets and capsules

Silybine (SBN), isosilybine (ISBN), silycristine (SCN), silydianine (SDN), and taxifoline (TXF) are the main active flavonoids commonly found in the dried fruits of Silybum marianum, Gaertner (Compositae). Concentrations of these compounds, except TXF, are usually expressed together as silymarin content. This paper describes a simple dissolution test developed to estimate silymarin (Sl) in pharmaceutical formulations. Five commercial products were tested using this new method (including tablets, sugar tablets, and capsules): two from Argentina, one from Brazil, one from Spain, and one from Italy. Results demonstrated that, provided the dosage form disintegrates, amounts dissolved range from 50 to 90% of the labeled value. Products were analyzed by high performance liquid chromatography (HPLC) and UV spectrophotometry.     

Comparative oral bioavailability of conventional propranolol tablets and a new controlled-absorption propranolol capsule

Abstract

The relative bioavailabilities of a new once-a-day propranolol formulation (Duranol) and conventional propranolol tablets (Inderal) were evaluated in six healthy male volunteers in a randomized balanced cross-over study. During the first treatment period, subjects were administered either a single 160 mg Duranol capsule at 9 a.m. or 80 mg Inderal at 9 a.m. and 9 p.m. Plasma propranolol concentrations were measured at 0, 2, 3, 4, 5, 6, 8, 10, 12, 13, 14, 15, 16, 24 and 36 hours after the 9 a.m. dose.

Mean peak plasma propranolol concentrations (Cmax) of 92.7 ng/ml at 2 hours and 53.9 ng/ml at 2.8 hours were recorded after administration of the first and second Inderal doses, respectively. After Duranol dosing, the Cmax of 85 ng/ml was not significantly different than the Inderal values; however, Duranol's tmax of 8 hours was significantly greater (p < 0.05) than either tmax recorded for Inderal. Compared to data obtained after administration of conventional propranolol tablets, mean propranolol concentrations were significantly lower at 2, 3 and 4 hours (p < 0.01) and significantly higher at 8, 10 and 12 hours (p < 0.05) after Duranol administration. The lengths of time plasma levels remained at 5, 10, 20, 30, 40, 50, 60, 70 and 80 ng/ml were not significantly different between the two products. In addition, the mean AUCs for Inderal and Duranol after 12 hours (380.2 vs 434.0 ng ml<^?1h, respectively), 24 hours (728.0 vs 728.8 ng ml^?1h, respectively), 36 hours (813.0 vs 826.8 ng ml^?1h, respectively), or from time 0 to infinity (838.6 vs 860.4 ng ml^?1h, respectively) were not significantly different.

These results indicate no loss in bioavailability despite a significantly prolonged absorption time for Duranol relative to conventional propranolol tablets. These results suggest that in the treatment of cardiovascular disorders an equivalent single dose of Duranol can be substituted for the daily requirements of conventional propranolol administered in divided doses.     

盐酸金刚烷胺片溶出度的测定

采用酸性染料比色法测定盐酸金刚烷胺片的溶出度,该法快速,简便,结果准确可靠。盐酸金刚烷胺在0.5～5μ犂.ml-1的浓度范围内,线性关系良好。线性方程为:A=967.26×10-2C+2.51×10-2(r=0.9994).平均回收率为:99.7%。该方法为控制盐酸金刚烷胺片的溶出度提供有效而简便的手段。     

Design and evaluation in vitro of controlled release mucoadhesive tablets containing chlorhexidine

This investigation deals with the development of buccal tablets containing chlorhexidine (CHX), a bis-bis-guanide with antimicrobial and antiseptic effects in the oral cavity, and able to adhere to the buccal mucosa to give local controlled release of drug. A mucoadhesive formulation was designed to swell and form a gel adhering to the mucosa and controlling the drug release into the oral cavity.

Some batches of tablets were developed by direct compression, containing different amounts of hydroxypropylmethylcellulose (HPMC) and carbomer; changing the amount ratio of these excipients in formulations, it is possible easily modulate the mucoadhesive effect and release of drug. The in vitro tests were performed using the USP 26/NF paddle apparatus, a specifically developed apparatus, and a modified Franz diffusion cells apparatus. This last method allows a simultaneous study of drug release rate from the tablets and drug permeation through the buccal mucosa.

Similar tests have also been carried out on a commercial product, Corsodyl gel^®, in order to compare the drug release control of gel with respect to that of the mucoadhesive tablet, as a formulation for buccal delivery of CHX. While the commercial formulation does not appear to control the release, the formulation containing 15% w/w methocel behaves the best, ensuring the most rapid and complete release of the drug, together with a negligible absorption of the active agent as required for a local antiseptic action in the oral cavity.     

Study of controlled-release floating tablets of dipyridamole using the dry-coated method

Dipyridamole (DIP), having a short biological half-life, has a narrow absorption window and is primarily absorbed in the stomach. So, the purpose of this study was to prepare controlled-release floating (CRF) tablets of dipyridamole by the dry-coated method. The influence of agents with different viscosity, hydroxypropylmethylcellulose (HPMC) and polyvinylpyrollidon K30 (PVP K30) in the core tablet and low-viscosity HPMC and PVP K30 in the coating layer on drug release, were investigated. Then, a study with a three-factor, three-level orthogonal experimental design was used to optimize the formulation of the CRF tablets. After data processing, the optimized formulation was found to be: 80?mg HPMC K4M in the core tablet, 80?mg HPMC E15 in core tablet and 40?mg PVP K30 in the coating layer. Moreover, an in vitro buoyancy study showed that the optimized formulation had an excellent floating ability and could immediately float without a lag time and this lasted more than 12?h. Furthermore, an in vivo gamma scintigraphic study showed that the gastric residence time of the CRF tablet was about 8?h.     

Preparation and in vivo evaluation of spray dried matrix type controlled-release microparticles of tamsulosin hydrochloride for orally disintegrating tablet

The objective of this study was to achieve an optimal formulation of spray dried matrix type controlled-release (MTCR) microparticles containing tamsulosin hydrochloride for orally disintegrating tablet. To control the release rate of tamsulosin hydrochloride, Acrylate-methacrylate copolymer (Eudragit(?) L-100 or Eudragit(?) S-100) and ethylcellulose were employed on the composition of MTCR microparticles. Physicochemical properties of MTCR microparticles such as particle size and SEM were characterized. Pharmacokinetic parameters of tamsulosin hydrochloride were evaluated in the rats after oral administration. MTCR microparticles were spherical microparticles of around 10 μm diameter with a corrugated surface. ODTs containing MTCR microparticles were disintegrated within 30 s and MTCR microparticles were able to control the release rate of tamsulosin hydrochloride following Fickian diffusion mechanism. The in vitro release rates of tamsulosin hydrochloride from MTCR microparticles were proportional to the ratio of Acrylate-methacrylate copolymer to ethylcellulose. Moreover, MTCR microparticles retarded the in vivo release rate of tamsulosin hydrochloride without reducing the bioavailability. Our results suggest that MTCR microparticles may be potential oral dosage forms to control the release and to improve the bioavailability of tamsulosin hydrochloride.     

Preparation and in vivo evaluation of spray dried matrix type controlled-release microparticles of tamsulosin hydrochloride for orally disintegrating tablet

The objective of this study was to achieve an optimal formulation of spray dried matrix type controlled-release (MTCR) microparticles containing tamsulosin hydrochloride for orally disintegrating tablet. To control the release rate of tamsulosin hydrochloride, Acrylate-methacrylate copolymer (Eudragit^® L-100 or Eudragit^® S-100) and ethylcellulose were employed on the composition of MTCR microparticles. Physicochemical properties of MTCR microparticles such as particle size and SEM were characterized. Pharmacokinetic parameters of tamsulosin hydrochloride were evaluated in the rats after oral administration. MTCR microparticles were spherical microparticles of around 10 µm diameter with a corrugated surface. ODTs containing MTCR microparticles were disintegrated within 30 s and MTCR microparticles were able to control the release rate of tamsulosin hydrochloride following Fickian diffusion mechanism. The in vitro release rates of tamsulosin hydrochloride from MTCR microparticles were proportional to the ratio of Acrylate-methacrylate copolymer to ethylcellulose. Moreover, MTCR microparticles retarded the in vivo release rate of tamsulosin hydrochloride without reducing the bioavailability. Our results suggest that MTCR microparticles may be potential oral dosage forms to control the release and to improve the bioavailability of tamsulosin hydrochloride.     

Formulation,characterization and clinical evaluation of propranolol hydrochloride gel for transdermal treatment of superficial infantile hemangioma

The objective of the present study is to formulate and characterize propranolol hydrochloride (PPL?·?HCl) gel, and to evaluate the efficacy of this formulation in transdermal treatment for superficial infantile hemangioma (IH). The transdermal PPL?·?HCl gel was prepared by a direct swelling method, which chose hydroxypropyl methylcellulose (HPMC) as the matrix and used terpenes plus alcohols as permeation enhancer. Permeation studies of PPL?·?HCl were carried out with modified Franz diffusion cells through piglet skin. Our results pointed to that among all studied permeation enhancers, farnesol plus isopropanol was the most effective combination (Q_24, 6027.4?±?563.1?μg/cm², ER, 6.8), which was significantly higher than that of control gel (p?相似文献   

Dissolution kinetics of iron in liquid zinc

In hot dip galvanizing, steel strip is coated by immersion in a bath of molten zinc. The principal reactions that occur at the steel/liquid zinc interface are (1) dissolution of iron and (2) nucleation and growth of intermetallic compounds. In order to improve the management of industrial galvanizing baths, it is essential to evaluate the flux of dissolved iron that diffuses into the bath from the sheet. For this purpose, a rotating disk device has been developed to study the dissolution and diffusion of iron in pure liquid zinc at the temperature usually employed in galvanizing baths (465°C). Since the dissolution reaction is controlled by diffusion under these conditions, the diffusion coefficient of iron in liquid zinc has been measured and found to be: D _Fe ^Zn(L) = (9.8 ± 0.1) × 10^–10 m²·s^–1     

Interaction of iron-chromium alloys containing 10 and 25 mass% chromium with liquid aluminium Part I Dissolution kinetics

The dissolution process of iron-chromium alloys containing 10 and 25 mass% Cr in an aluminium melt at 700°C is found by the rotating-disc technique to be diffusion-controlled and non-selective. Experimentally determined values of the saturation concentration (solubility) and the dissolution rate constant of iron and chromium in liquid aluminium for the Fe—Cr alloys are presented. Evaluated values of the diffusion coefficients of Fe and Cr across the diffusion boundary layer into the melt are also given.     

Release of cyclobenzaprine hydrochloride from osmotically rupturable tablets

Osmotically rupturable systems were developed and the release of cyclobenzaprine hydrochloride (model drug) from the systems was investigated. Systems were designed using mannitol (osmotic agent) and increasing amounts of polyethylene oxide (PEO, a water-swellable polymer) surrounded by a semipermeable membrane. When placed in an aqueous environment, osmotic water imbibition into the systems distended and swelled the systems until the membrane ruptured and released the active compound to the outside environment. Tablets with increasing amount of PEO exhibited longer rupture times. This may be due to osmotic pressure-modulating properties of the polymer, changing the rate of water imbibition into the systems.

The integrity of the membranes was investigated using high-pressure mercury intrusion porosimetry. Minimal mercury intrusion into the membrane structure and core tablet indicated membrane integrity and lack of defective areas or pinholes. The results were in agreement with the release profiles where no drug release was detected prior to membrane rupture. Mercury intrusion porosimetry appears to be a promising technique for evaluation of membrane integrity.

Once the systems ruptured, drug was released by osmotic pumping and diffusion mechanisms through the ruptured area. There was a decrease in drug release rate with inclusion of PEO in the core.

The effects of film thickness on rupture and release times were also investigated. Devices with thicker films produced longer rupture times. This is in agreement with the theoretical prediction.     

Comparative dissolution of commercuially available hydroxyzine hydrochloride tablets

A comparative dissolution study was conducted on commercially available hydroxyzine hydrochloride tablets using USP Apparatus 2 (Paddle Method) at 50 rpm and two dissolution media: Water and Simulated Intestinal Fluid (SIF) and the USP recommended method employing the disintegration apparatus. The dissolution characteristics of 22 samples of hydroxyzine hydrochloride tablets representing four dosage levels and seven manufacturers were profiled.

The study illustrated that the Modified Disintegration apparatus is not able to distinguish slow dissolving formulations from fast dissolving formulation and, consequently, does not provide assurance of bioequivalence and does not perform as an adequate manufacturing control to insure lot to lot uniformity.