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

Abstract

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 microm) were considered optimal for 24-hour lasting dissolution of DS.

In situ fluidized hot melt granulation using a novel meltable binder: Effect of formulation variables on granule characteristics and controlled release tablets

“…However, the variation in the percentage of meltable binder modified release profiles, especially when glyceryl palmitostearate was decreased from 20% to 10% (f 1 = 39.7 and f 2 = 29.5 for Formulation 2/Formulation 1 and f 1 = 16.8 and f 2 = 59.7 for Formulation 2/Formulation 3). As expected, a higher percentage of lipophilic binder was associated with a lower drug release [19,34]. The increase in glyceryl palmito-stearate also implied a corresponding decrease in lactose composition (Table 1).…”

A review on recent developments in binder jetting metal additive manufacturing: materials and process characteristics

“…Thus, more extensively used qualitative indexes for measuring the flowability and packability of powders are the Hausner ratio and Carr indexes, which give a cheap and fast preliminary idea of powder behaviour. Although both indexes have been criticised for lack of theoretical basis and for being uncomplete methodologies for the correct characterisation of powder flowability for AM purposes [39], they give an empirically tested accurate qualitative value of powder processability [42][43][44]. Table 1 shows some data from the study of the influence of bimodal size powders in BJ performed by Bai et al [45], in which the Hausner ratio is calculated for different Cu powder and their mixtures.…”

Oxycellulose Beads with Drug Exhibiting pH-Dependent Solubility

“…It is slightly soluble in water, sparingly soluble in phosphate buffer (PB) solutions of pH 6.8 (DS solubility 670 μg/ml) and 7.2. Because DS is practically insoluble in hydrochloric acid of pH 1.2 (23,24), OC particles are expected to by-pass the gastric environment and start to release the drug in the intestine where the pH of the intestinal content is more favourable. Thus, undesirable side effects of DS on gastric mucosa are minimized (25).…”