Effect of montmorillonite on drug release from polymeric matrices

Drug release from matrices of polyvinyl alcohol was affected by molecular weight and solubility of the drugs (either sodium salicylate or papaverine hydrochloride), and by the matrix loading. - Montmorillonite addition to the matrix formulation modified only the release constant of papaverine hydrochloride owing to drug interaction with the clay by an ionic exchange process. The kinetics exponent was affected a little bit by interaction of the drug with montmorillonite, whereas the influence of the matrix loading was more remarkable.     

Controlled release captopril microcapsules: effect of non-ionic surfactants on release from ethyl cellulose microcapsules

Captopril microcapsules were prepared with different viscosity grades of ethyl cellulose by temperature induced coacervation from cyclohexane. Both non-ionic surfactants or their combinations and 2 per cent absolute alcohol as cosolvent were added to the coacervation system to ensure complete solvation of the ethyl cellulose and efficient microencapsulation of the drug. The in vitro dissolution was studied in 0.1 N hydrochloric acid. Microcapsules prepared using 2 per cent Tween 80 with ethyl cellulose of 41 c.p. viscosity grade exhibited the most prolonged release with a t70 per cent of 55 min in comparison to 7.75 min for control microcapsules prepared without surfactant. Different kinetic models have been used to explain the release. The best fit with the highest correlation coefficients was the first-order kinetics plot with two straight lines having two different slopes. The initial slope presents the faster release rate than the terminal slope. This fast release would be useful for the initial dose of the prolonged release formulation.     

卡托普利控释微丸的研制

目的：制备卡托普利控释微丸，并对其释药情况进行研究。方法：在流化床内，用丙烯酸树脂RL30D和丙烯酸树脂RS30D的混合物作为包衣材料制备卡托普利控释微丸，对包衣材料配比及包衣材料用量进行选择，对微丸体外释药方程进行研究，采用加速试验法考察微丸释药稳定性。结果：包衣材料最佳配比丙烯酸树脂RL30D-丙烯酸树脂RS30D为1：5，包衣材料最佳用量为包衣增重20％，微丸的体外释药方程为Q＝0．09614t-0．008379(r＝0．9980)，释药稳定性好。结论：卡托普利控释微丸具有良好的零级释药特征。     

Effect of antioxidants on captopril floating matrices

Stability of captopril in a controlled release formulation has been a challenge for some time. The sustained release of captopril from floating matrices has been studied varying the antioxidant load, the sodium bicarbonate proportion and the compaction pressure. Although in many cases the effect of compaction pressure remains hidden, actual results show that matrices compacted at 55?MPa have smaller density and float in the dissolution medium while those compacted at 165?MPa float only adding sodium bicarbonate. The increase of compaction pressure reduces the hydration volume and increases the time necessary to attain its maximum. These changes are attributed to lower matrix porosity and to the consequent diminution of water and drug transport. Increasing ascorbic acid proportions increase the matrix hydration volume and the drug released. The use of sodium ascorbate and the substitution of 15% polymer with sodium bicarbonate reduce the matrix hydration volume, shorten the matrix hydration process and increase the drug released. This is attributed to carbon dioxide bubbles that decrease the matrix coherence and expand the matrix volume, facilitating drug dissolution and only a limited further matrix expansion. The antioxidant protection provided by sodium ascorbate was lesser of that of ascorbic acid because of greater molecular mass and lesser release rate.     

Effect of antioxidants on captopril floating matrices

Stability of captopril in a controlled release formulation has been a challenge for some time. The sustained release of captopril from floating matrices has been studied varying the antioxidant load, the sodium bicarbonate proportion and the compaction pressure. Although in many cases the effect of compaction pressure remains hidden, actual results show that matrices compacted at 55?MPa have smaller density and float in the dissolution medium while those compacted at 165?MPa float only adding sodium bicarbonate. The increase of compaction pressure reduces the hydration volume and increases the time necessary to attain its maximum. These changes are attributed to lower matrix porosity and to the consequent diminution of water and drug transport. Increasing ascorbic acid proportions increase the matrix hydration volume and the drug released. The use of sodium ascorbate and the substitution of 15% polymer with sodium bicarbonate reduce the matrix hydration volume, shorten the matrix hydration process and increase the drug released. This is attributed to carbon dioxide bubbles that decrease the matrix coherence and expand the matrix volume, facilitating drug dissolution and only a limited further matrix expansion. The antioxidant protection provided by sodium ascorbate was lesser of that of ascorbic acid because of greater molecular mass and lesser release rate.     

The effect of various surfactants on the release rate of propranolol hydrochloride from hydroxypropylmethylcellulose (HPMC)-Eudragit matrices.

Hydrophilic and lipophilic polymers are widely used excipients to control the release rate of drugs from matrices. Researchers found that surfactants are able to control the release rate of drugs. The aim of the present investigation is to determine the effects of surfactant type, its concentration and the different ratios of surfactants on the release rate of highly soluble drug (propranolol HCl). In this study, sodium lauryl sulphate (SLS) as an anionic surfactant, cetyl trimethyl ammonium bromide (CTAB) as a cationic surfactant, Tween 65 and Arlacel 60 as non-ionic surfactants were selected. The different concentrations of surfactants were incorporated into hydroxypropylmethylcellulose-Eudragit matrices and then dissolution rate of the drug from the matrices were evaluated at pH 1.2 or 6.8. The results showed that the release rate of propranolol decreased as the concentration of SLS increased. This is due to that SLS is able to form complex with propranolol. In contrast Tween 65 caused an increase in the release rate of the drug. Cationic surfactant (CTAB) had little effect on the release rate of the drug. It was shown that as the ratio of CTAB:SLS increased the release rate of propranolol increased from matrices. This indicated that as CTAB is able to interact with SLS molecules, therefore number of the interacting anionic molecules with the cationic drug was decreased. It can be concluded that, the type and ionization of surfactant, hydrophilicity and lipophilicity of surface active agent and various ratios of surfactants are important factors in controlling the release rate of propranolol.     

Effect of film composition and various penetration enhancers concentrations on prazosin release from acrylic polymeric film

An investigation was conducted to evaluate the effect of changing the Eudragit RL 100 ratio and the influence of different penetration enhancers in various concentrations on the release of prazosin from Carboset 525:Eudragit RL 100 polymeric films using improved Franz diffusion cells, to choose the most suitable polymeric film ratio, the most appropriate enhancer and its optimum concentration to be used to achieve the maximum release of the drug. The results show that prazosin release from polymeric films containing Carboset 525:Eudragit RL 100 in a 1:1 ratio was significantly (p < 0.05) higher than from films in a 1:0.25 ratio and non-significantly (p > 0.05) higher than from those containing 1:0.5, 1:3 polymer ratios and non-significantly lower from those containing 1:4 polymer ratios. The addition of various enhancers, n-decyl alcohol (7, 9 and 11% w/w), Azone (4, 6 and 8% w/w) and Cineole (7, 9, 11 and 14% w/w) significantly (p < 0.05) enhanced the prazosin release from these polymeric films containing the two polymers in a 1:1 ratio. The best concentrations of these enhancers were 11% n-decyl alcohol, 9% Cineole and 8% Azone. The formulations containing these concentrations of the enhancers are being further studied for drug release through rabbits skin. It was found that using either of these enhancers in these concentrations resulted in a significant (p < 0.05) increase in the amount of prazosin transported across the skin. On the other hand these enhancers did not show any significant (p > 0.05) difference between them. The mechanism of drug release from the polymeric films was further studied using water vapor permeability (W.V.P.), the permeability constant (P) and differential scanning calorimetry. The enhancers were found to increase the W.V.P. and the permeability constant (P) and the results were in very good agreement with the effect of enhancers on the in-vitro drug release. The DSC thermograms showed that the enhancers physically interacted with either or both of the polymeric film materials and prazosin which could be one of the reasons for the improvement in the release of the drug from these polymeric films.     

The role of various surfactants on the release of salbutamol from suppositories

Salbutamol is a selective beta(2)-adrenoreceptor agonist with different pharmacological effects. In this research because of the simplicity of suppository application in elderly and its higher plasma concentration than tablets as well as its particular indication in premature labour, salbutamol suppositories were prepared. The suppositories were formulated containing 10 mg of the drug and Witepsol H15, the oleaginous soluble base using melting method. To optimize the release rate of drug, different surfactants namely, sodium lauryl sulphate (SLS) as an ionic surfactant and Tween 80 as well as Arlacel 60 as non-ionic surfactants with different HLBs were chosen. The effect of surfactant concentration on the release rate of salbutamol from suppositories were also investigated. All prepared formulations fulfilled the specifications set down in British Pharmacopoeia. The results showed that Tween 80 (2%w/w) and SLS (0.75%w/w) caused an increase in dissolution rate of salbutamol from suppositories. As anionic surfactants, such as SLS, cause greater damage on mucosa than non-ionic surfactant, such as Tween 80, this study recommended that Tween 80 could be added in suppository formulation in order to increase the dissolution rate of salbutamol. It was also shown that the release rate of salbutamol altered linearly with the amount of Tween 80 in suppository formulations.     

Effect of plasticization on heparin release from biodegradable matrices

Heparin-loaded polymer films of poly-L-lactide (PLLA) and poly-L-lactide-co-glycolide (PLLGA) as well as poly-DL-lactide-co-glycolide (PLGA) were produced. A plasticizer, PEG, was added to the polymers. It was found that the release profile in general consisted of a burst effect, a diffusion-controlled phase and a degradation-controlled phase. The plasticizer accelerated the onset of degradation in all cases, but its effect on the release profile differed significantly depending on the polymer. The plasticizer depressed the burst effect for PLLA, and accelerated the kinetics of the diffusion-controlled phase. For the PLLGA 80/20, however, the plasticizer had no significant effect on the release profile or kinetics. We explain these observations in terms of hydrophilicity and crystallinity effects.     

卡托普利渗透泵型控释片的药代动力学

目的研究卡托普利渗透泵型控释片在家犬体内的药代动力学。方法以卡托普利普通片为对照 ,应用HPLC法测定血药浓度。结果卡托普利渗透泵型控释片和普通片的tmax分别为 5 5h和 1 5h ,t1/ 2 分别为 6 73h和 3 5 2h ,ρmax分别为 85 5 1和 172 5 3μg·L-1。相对生物利用度为(119 2 0± 2 3 2 0 ) %。结论渗透泵控释片血药浓度平稳 ,可较长时间保持有效血药浓度     

Effect of chemical properties on drug release from hydrophobic matrices

The drug release of modified release matrix systems is often governed by erosion as well as by diffusion through the matrix. The purpose of the present work was to study the release kinetic parameters of inorganic and organic water soluble drugs from hydrophobic wax matrix systems, produced by melt coating. The drug release process was investigated both experimentally and by means of mathematical models. Different models (first order, cube root, square root, two-third root) and the Weibull distribution were applied for the evaluation of the drug release data. On the basis of our results, it can be concluded that not only the ratio but the chemical characteristic of the drug and the matrix base material as well determine the rate of drug release.     

The influence of concentration on the release of drugs from gels and matrices containing Methocel

The release of propranolol hydrochloride from hydroxypropylmethylcellulose and methylcellulose matrices has been examined at constant cellulose ether contents. As the drug content decreased, the release rate of propranolol became disproportionately higher. HPMC K4M, HPMC F4M and HPMC E4M all performed similarly. However, with methylcellulose matrices, a burst release at low drug levels was apparently due to a failure of the matrix to maintain integrity. Explanations were sought on the basis of diffusional studies. Apparent diffusion coefficients were in the order of 3.1–3.8 × 10⁻⁶ cm² s⁻¹ for propranolol hydrochloride. Each of the four grades performed similarly. Using similar diffusional studies, but HPMC K15M as the polymer, an apparent diffusion coefficient of 3.6 × 10⁻⁶ cm² s⁻¹ was derived, indicating that the coefficient was independent of molecular weight. The coefficient was dependent on HPMC content decreasing from approx. 5.5 × 10⁻⁶ to 3 × 10⁻⁶ cm² s⁻¹ as the HPMC content was increased from 5 to 15% w/w. The diffusion coefficients of tetracycline hydrochloride were lower and conversion to the free base is postulated as the explanation of previously described anomolous release for this drug from matrix tablets. The tortuosity of the gels was independent of the included drug.     

Study of the prolonged release of theopylline from polymeric matrices based on grafted chitosan with acrylamide

The aim of this work was to study the performance of chitosan (CB) grafted with acrylamide (CB-g-A) as prolonged drug release matrix as compared with unmodified chitosan. A non-pH dependent swelling behaviour for the matrix tablets based on grafted chitosan was observed. The overlaping between degree of swelling measured by weighing (DSw) and measured by increase of diameter (DSd) up to 240 minutes showed that the swelling process could be isotropic. The non-pH dependent swelling behaviour of these matrices could be explained by the partial substitution of amine groups of the chitosan chain by acrylamide. The grafting reaction provides an ionizable amine group by a neutral amide group which make the matrix non pH-dependent. On the contrary, the matrix tablet based on chitosan showed a pH dependent swelling behaviour where the swelling process could be anisotropic. The higher degree of erosion and swelling of the formulation based on CB-g-A600 (%G = 600) compared with the formulation based on chitosan and CB-g-A418 (%G = 418) could explain the higher fraction of theopylline released. For all formulations studied in this work, the amount of theopylline released from the matrix tablets was found to be controlled by a combination of the diffusion process and relaxation of the polymeric structure. These results match with the controlled swelling behaviour and low degree of erosion observed for these systems.     

Dense gas processing of polymeric controlled release formulations

Dense gas techniques, which utilize the properties of fluids in the vicinity of their critical points, are of increasing interest in the processing of pharmaceuticals. It is generally known that dense gases can be used for extractions, chromatographic separations and chemical synthesis due to their liquid-like solvation power and gas-like mass-transfer properties. The processes can be conducted at moderate operating conditions and are thus suitable for many heat-labile compounds such as proteins, biocompatible polymers and pharmaceuticals. Recent applications of dense gas techniques include micronization, crystallization of high-purity particles, sterilization and preparation of microencapsulated drug formulations. The following paper provides a brief overview of dense gases and various processing techniques to fabricate polymeric drug-loaded formulations for controlled release purposes.     

Factors effecting drug release from inert matrices. Part 1: effects of surfactants on the release of quinine sulfate.

Dissolution rate studies of quinine sulfate from polyamide matrices, in simulated gastric and intestinal fluids, are carried out in the presence of hexadecyltrimethylammonium bromide, sodium lauryl sulfate and polyoxyethylene (50) stearate surfactants. The results obtained show that dissolution rate is dependent upon the pH of the disolution media and the type and concentration of surfactant. The solubilization effect of surfactants is also examined and the findings are discussed.     

Sustained release from inert matrices I. Effect of macrocrystalline cellulose on aminophylline and theophylline release

The release of aminophylline and theophylline embedded in a matrix composed of different ratios of microcrystalline cellulose and glyceryl monostearate (or propylene glycol monostearate) was investigated. The result indicated that drug release within a certain period follows a diffusion-controlled matrix model, where the drug quantity released was proportional to the square root of time. The release rate was found to increase with increasing microcrystalline cellulose—glyceryl monostearate ratio. The logarithm of the rate constant was proportional to the fraction of microcrystalline cellulose in the matrix. The tablets prepared using solvent-evaporated matrix showed quicker release than those prepared from fused ones. Propylene glycol monostearate achieved similar, but somewhat quicker release, than glyceryl monostearate.     

In vitro-in vivo correlation and bioavailability studies of captopril from novel controlled release donut shaped tablet

A controlled release formulation of captopril which was coated and fabricated into a donut shaped tablet formulation, was investigated in rabbit for pharmacokinetic and in vitro-in vivo correlation studies. Coated donut shaped tablets were prepared and in vitro release was studied in simulated gastric fluid at three different RPMs. New Zealand albino male rabbits have been used as animal model for in vivo study. A sensitive and simple HPLC method was developed for the determination of captopril content in rabbit plasma. In vitro release studies showed that release patterns followed zero order for around 4 h. Single oral administration of coated donut shaped tablets in rabbit illustrated retained availability of captopril to the injected drug. Captopril content could pursue the same release pattern over the same time course in in vivo study. The in vivo-in vitro correlation coefficients obtained from point-to-point analysis were greater than 99% between concentrations at certain time points obtained from release study in simulated gastric fluid at different RPMs and HPLC analysis of rabbit's plasma. From the in vitro-in vivo correlation prediction it was evident that the coated donut shaped tablet is a good device for controlled delivery of captopril.     

Core-modified chitosan-based polymeric micelles for controlled release of doxorubicin

Amphiphilic stearic acid-grafted chitosan oligosaccharide (CSO-SA) micelles have been shown a good drug delivery system by incorporating hydrophobic drugs into the core of the micelles. One of the problems associated with the use of CSO-SA micelles is disassociation or the initial burst drug release during the dilution of drug delivery system by body fluid. Herein, the core of CSO-SA micelles was modified by the physical solubilization of stearic acid (SA) to reduce the burst drug release and enhance the physical stability of CSO-SA micelles. The CSO-SA micelles had 27.4+/-2.4 nm number average diameter, and indicated pH-sensitive properties. The micelle size and drug release rate from micelles increased with the decrease of pH value. After the incorporation of SA into CSO-SA micelles, the micelle size was increased, and the zeta potential was decreased. The extents of the increase in micelle size and the decrease of zeta potential related with the incorporated amount of SA. The in vitro drug release tests displayed the incorporation of SA into CSO-SA micelles could reduce the drug release from the micelles due to the enhanced hydrophobic interaction among SA, hydrophobic drug and hydrophobic segments of CSO-SA.