The influence of formulation on the dissolution profile of diclofenac sodium tablets

In attempts to design delayed-release tablets of diclofenac sodium, seven experimental batches were produced. The influence of super-disintegrant croscarmellose sodium (CCS), the granulation process, and the thickness of Eudragit® L 100 coating film were evaluated. The values of dissolution efficiency and the similarity factor were used to compare the dissolution profiles of each experimental batch and the reference Voltaren®. Both methods appear to be applicable and useful in comparing dissolution profiles. Based on such values four batches were considered similar when contrasted with the reference. The results suggest an optimal relationship between the amount of CCS and the thickness of the coating film, which provides appropriate dissolution rate of diclofenac sodium from the dosage forms.     

Soluble filler as a dissolution profile modulator for slightly soluble drugs in matrix tablets

The purpose of this experimental work was the development of hydrophilic–lipophilic matrix tablets for controlled release of slightly soluble drug represented here by diclofenac sodium (DS). Drug dissolution profile optimization provided by soluble filler was studied. Matrix tablets were based on cetyl alcohol as the lipophilic carrier, povidone as the gel-forming agent, and common soluble filler, that is lactose or sucrose of different particle size. Physical properties of tablets prepared by melt granulation and drug release in a phosphate buffer of pH 6.8 were evaluated. In vitro studies showed that used filler type, filler to povidone ratio and sucrose particle size influenced the drug release rate. DS dissolution profile could be changed within a wide range from about 50% per 24 hours to almost 100% in 10 hours. The release constant values confirmed that DS was released from matrices by the diffusion and anomalous transport. The influence of sucrose particle size on the drug release rate was observed. As the particle size decreased, the drug release increased significantly and its dissolution profile became more uniform. Soluble fillers participated in the pore-forming process according to their solubility and particle size. Formulations containing 100 mg of the drug, 80 mg of cetyl alcohol, 40 mg of povidone, and 80 mg of either lactose or sucrose (particle size 250–125 μm) were considered optimal for 24-hour lasting dissolution of DS.     

Eudragit and hydrotalcite-like anionic clay composite system for diclofenac colonic delivery

In this paper, the microencapsulation of the MgAl-hydrotalcite (HTlc) and diclofenac (DIK) intercalation product (HTlc-DIK) was realized in order to obtain a composite system for colonic drug delivery. Eudragit^® S or Eudragit^® L were used as polymers for preparation of microparticles (MPs). MPs were prepared by using a properly modified oil-in-oil solvent evaporation method. A 1:5 or 1:10 w/w HTlc-DIK/polymer ratios were employed. An experimental design was applied in order to assess the preparation variable effects on the qualitative MP appearance. Improved MP preparations were achieved when 7–13 ml of acetone-ethanol solution was employed at both HTlc-DIK/polymer ratios. The MPs were tested for in vitro drug release. DIK release from Eudragit^® L MPs at pH 6.8 reached 26–35% within 25–30 min at both HTlc-DIK/polymer ratios and no further increase was observed when the pH was shifted to 7.5. DIK release from Eudragit^® S MPs at pH 7.5 reached for both ratios 70% after 6–8 h.The obtained results showed that hydrotalcite intercalation compound can be microencapsulated without missing the intercalated compound and the resulted composite MPs showed good characteristics. Besides HTlc-DIK/Eudragit^® S MPs possess improved features with respect to HTlc-DIK/Eudragit^® L MPs. For this reason, HTlc-DIK/Eudragit^® S MPs could be promising for drug delivery either to the distal part of small intestine or to the colon.     

Application of Ozone Involving Advanced Oxidation Processes to Remove Some Pharmaceutical Compounds from Urban Wastewaters

Different UVA radiation and advanced oxidation systems, most of them involving ozone, have been applied to remove mixtures of three contaminants of pharmaceutical type: diclofenac (DCF), sulfamethoxazole (SMT) and caffeine (CFF), both in ultrapure and secondary treated wastewater. The influence of the water matrix has been studied in terms of individual compound concentration and TOC removal. Also, biodegradability of the treated wastewater before and after the advanced oxidation process, as BOD/COD ratio, the partial oxidation yield, the increment of average state of carbon oxidation and ozone consumption have been determined. For mgL^?1 to 100 μgL^?1 concentrations and regardless of the ozone process and water type, DCF and SMT are removed in less than 10 min mainly by direct reaction with ozone, especially in the case of DCF. CFF, on the contrary, is mainly removed through hydroxyl radicals. For lower concentration (≤100 μgL^?1), DCF still disappears by direct ozonation, CFF by hydroxyl radicals oxidation and SMT through both direct ozonation and hydroxyl radical oxidation. Once DCF and SMT have disappeared, TOC is removed by reacting with hydroxyl radicals, regardless of the water matrix. Photocatalytic ozonation allows the highest TOC degradation rate, partial oxidation yield, increment of average state of carbon oxidation and biodegradability together to the lowest ozone consumption per mg TOC eliminated.     

Diclofenac release from polycaprolactone 3D matrices produced by electrospinning: influence of fiber structure and composition of the surrounding medium

Abstract

The release of tritium-labelled diclofenac from 3D matrices produced by electrospinning from polycaprolactone or PCL blends with human serum albumin in hexafluoroisopropanol was studied. Diclofenac is released significantly faster from matrices made from PCL solution with 10% HSA than from matrices made from pure PCL. Diclofenac was also released faster into blood plasma than into PBS, and the presence of diclofenac in the medium reduced the release rate, as indicated by experiments with regular medium replacement. Thus, diclofenac release depends on the composition of electrospinning solution, the nature of the external medium and the diclofenac concentration in the external medium.     

双氯芬酸钾软膏的制备及其体外累积释药率的测定

制备双氯芬酸钾软膏并且应用Franz扩散池法测定其在不同测定温度和接收介质中的体外累积释药率,结果显示在测定温度为37℃、接收介质为磷酸盐缓冲液(pH=7.0)时软膏的累积释药率高达90%以上,透皮速率为2.08μg·cm-2·h-1,可以达到实验设计的目的.     

Formulation and Evaluation of Diclofenac Sodium Using Hydrophilic Matrices

Controlled-release tablets (having near zero-order release) of diclofenac sodium, a water-soluble drug, were prepared using hydrophilic polymers like hydroxypropylmethylcellulose (HPMC), sodium carboxymethylcellulose (NaCMC), and Carbopol 934. Tablets were also prepared with mixtures of polymers of NaCMC, HPMC, and Carbopol 934. The optimum ratio of drug : HPMC : NaCMC was found to be 1 : 2 : 1. A combination of nonionic polymer HPMC and anionic NaCMC polymer matrix resulted in near zero-order release of diclofenac sodium. The results obtained were in agreement with the earlier reports. It is observed that increasing polymer content produces more sustained effect. A combination of nonionic polymer HPMC and anionic polymer NaCMC as the polymer matrix resulted in near zero-order release of diclofenac sodium. Drug release from the matrix did not follow Fick's law of diffusion and exhibited near zero-order release. Results of the bioavailability studies indicated that formulation 4 with drug : HPMC : NaCMC equal to 1 : 2 : 1 was similar to the marketed product Dicloran SR and showed better bioavailability than Voveran SR. A statistically significant difference was seen between Voveran SR and the other two products. A good in vitro–in vivo correlation was observed for these products.     

Sustained Release of Diclofenac from Polymer-Containing Suppository and the Mechanism Involved

Sustained release of diclofenac sodium (DcNa) from suppositories composed of triglycerides and polymer was investigated by dissolution testing through an artificial membrane. DcNa was slowly released from a suppository containing carboxyvinyl polymer (CVP), and the extent of the release decreased with the amount of CVP added. Little effect was noted with the addition of other water-soluble polymers, such as hydroxyethylcellulose (HEC), xanthan gum, and polyvinylalcohol (PVA). When sodium benzoate was used instead of DcNa, a similar result was obtained with the addition of CVP. The result of release rate analysis together with the viscosity and pH in these cases showed that the reduction of solubility and diffusion due to sodium exchange between DcNa and CVP played an important role in the sustained release from the suppository. Also, in comparison with the results when CVP was not used, the plasma concentration profile of diclofenac after the administration of CVP suppository displayed a twofold longer half-life time.     

Effect of Formulation Composition on the Properties of Controlled Release Tablets Prepared by Roller Compaction

This study discusses the effect of formulation composition on the physical characteristics and drug release behavior of controlled‐release formulations made by roller compaction. The authors used mixture experimental design to study the effect of formulation components using diclofenac sodium as the model drug substance and varying relative amounts of microcrystalline cellulose (Avicel), hydroxypropyl methylcellulose (HPMC), and glyceryl behenate (Compritol). Dissolution studies revealed very little variability in drug release. The t₇₀ values for the 13 formulations were found to vary between 260 and 550 min. A reduced cubic model was found to best fit the t₇₀ data and gave an adjusted r‐square of 0.9406. Each of the linear terms, the interaction terms between Compritol and Avicel and between all three of the tested factors were found to be significant. The longest release times were observed for formulations having higher concentrations of HPMC or Compritol. Tablets with higher concentrations of Avicel showed reduced ability to retard the release of the drug from the tablet matrix. Crushing strength showed systematic dependence on the formulation factors and could be modeled using a reduced quadratic model. The crushing strength values were highest at high concentrations of Avicel, while tablets with a high level of Compritol showed the lowest values. A predicted optimum formulation was derived by a numerical, multiresponse optimization technique. The validity of the model for predicting physical attributes of the product was also verified by experiment. The observed responses from the calculated optimum formulation were in very close agreement with values predicted by the model. The utility of a mixture experimental design for selecting formulation components of a roller compacted product was demonstrated. These simple statistical tools can allow a formulator to rationally select levels of various components in a formulation, improve the quality of products, and develop more robust processes.     

A new controlled-release liquid delivery system based on diclofenac potassium and low molecular weight chitosan complex solubilized in polysorbates

A complex of low molecular weight chitosan (LMWC) with oleic acid and diclofenac potassium (DP) was prepared and dispersed in high concentrations of polysorbate 20, 60 and 80 in water to form a solution which releases its components slowly. The formed complex was characterized using different analytical methods. The size of the resulted nanoparticles and the effect of tweens on size were followed using dynamic light scattering (DLS). The release of DP from this delivery system was monitored by altering the molecular weight of chitosan and the type and concentration of the polysorbates used. The most suitable preparation consisted of DP, LMWC 13?kDa, and oleic acid. This was dispersed in 5% Tween 80 and the release was followed by the adaptation of USP II apparatus using a cellophane bag. This preparation offers a release of up to 24?h.