Excipient In Matrix Tablets Research Articles

Saturated phosphatidylcholine as matrix former for oral extended release dosage forms

The aim of this study was to evaluate the suitability of saturated phosphatidylcholine (Phospholipon® 90H) as extended release excipient in matrix tablets for three model drugs with different aqueous solubility (theophylline, caffeine and diprophylline). The tablets could be prepared by direct compression because of the favorable phospholipid powder flow properties (Carr's index: 12.64 and angle of repose: 28.85) and good compactibility. Tablets of low porosity were formed already at low pressure of 40MPa and with drug loadings up to 70% due to high plasticity of the phospholipid. Extended drug release was achieved with the drugs of different solubility and at various drug loadings. For example, the caffeine release time (t80%) from 8mm tablets ranged from 1.5h to 18h at 70% and 10% drug loading, respectively. The drug release was governed by diffusion and could therefore be modelled by Fick's law of diffusion. Drug release profiles were thus a function of drug solubility, drug loading and tablet dimension. Matrix tablets of caffeine (20% drug loading) showed robust dissolution with regard to agitation (50–100rpm) and ionic strength of the release media (100–600 mOsmol/kg). Caffeine release was pH-dependent with a faster drug release at acidic pH, which was attributed to a protonization of the phosphatidyl group of the matrix-former and thus a higher hydrophilicity.

Evaluation of sesamum gum as an excipient in matrix tablets

In developing countries modern medicines are often beyond the affordability of the majority of the population. This is due to the reliance on expensive imported raw materials despite the abundance of natural resources which could provide an equivalent or even an improved function. The aim of this study was to investigate the potential of sesamum gum (SG) extracted from the leaves of Sesamum radiatum (readily cultivated in sub-Saharan Africa) as a matrix former. Directly compressed matrix tablets were prepared from the extract and compared with similar matrices of HPMC (K4M) using theophylline as a model water soluble drug. The compaction, swelling, erosion and drug release from the matrices were studied in deionized water, 0.1 N HCl (pH 1.2) and phosphate buffer (pH 6.8) using USP apparatus II. The data from the swelling, erosion and drug release studies were also fitted into the respective mathematical models. Results showed that the matrices underwent a combination of swelling and erosion, with the swelling action being controlled by the rate of hydration in the medium. SG also controlled the release of theophylline similar to the HPMC and therefore may have use as an alternative excipient in regions where Sesamum radiatum can be easily cultivated.

Formulation and development of ternary hybrid matrix tablets of diltiazem hydrochloride

Polyethylene oxide (PEO) has been extensively used as an extended-release excipient in matrix tablets due to its extraordinarily safe, stable, soluble, swellable and erodible properties. The present study aimed to develop once-daily sustained-release tablets using PEO for a highly water-soluble drug, diltiazem hydrochloride (DH), the clinical application of which is limited because of its short half-life in vivo. However, the prophase study demonstrated that the use of PEO alone could only retard the drug release to 8h. Thus, we proposed its combined use with chitosan/sodium alginate and formulated ternary matrix tablets by direct compression, in the hope of further extending the release of DH. The in vitro release study demonstrated that the ternary matrix synergistically prolonged DH release to 24h while the kinetic mechanism study showed that its release was correlated with Korsmeyer–Peppas models and a non-Fickian drug release mechanism. Its release was primarily governed by diffusion and secondarily by erosion. The results of the present study demonstrated for the first time the feasibility of using a ternary hybrid matrix to prolong the release of highly water-soluble drugs, at least in the case of DH, which has a solubility as high as 625mg/mL.

Ultrasound Effect on Swelling Properties and Drug Release Behaviors of Spray-Dried Tapioca Starch Tablets

Modified starches have been widely used as an excipient in matrix tablets to control drug release. A new processing method for the production of modified starch, high power ultrasonic treatment (400 W), was applied to native tapioca starch. The spray drying technique was used after modification (i.e., by ultrasonic or heat treatment). Matrix tablets were then prepared by direct compression using theophylline as a model drug. The effect of starch modification on swelling, erosion and in vitro drug release behaviors of compressed matrices was investigated in 0.1 N HCl or phosphate buffer (pH 6.8). The matrix tablets of modified tapioca starch formed a continuous gel layer while in contact with the aqueous medium undergoing a combination of swelling and erosion. The ultrasound-treated starch swelled and eroded less than the native starch and heat-treated starch, thus the drug release from matrix tablets using ultrasound-treated starch was slower. For these results, it can be concluded that the ultrasound-treated starch was a promising excipient for controlled drug release.

Graft copolymers of ethyl methacrylate on waxy maize starch derivatives as novel excipients for matrix tablets: Drug release and fronts movement kinetics

A previous paper [1] deals with the physicochemical and technological characterization of novel graft copolymers of ethyl methacrylate (EMA) on waxy maize starch (MS) and hydroxypropylstarch (MHS). The results obtained suggested the potential application of these copolymers as excipients for compressed non-disintegrating matrix tablets. Therefore, the purpose of the present study was to investigate the mechanism governing drug release from matrix systems prepared with the new copolymers and anhydrous theophylline or diltiazem HCl as model drugs with different solubility. The influence of the carbohydrate nature, drying procedure and initial pore network on drug release kinetics was also evaluated. Drug release experiments were performed from free tablets. Radial drug release and fronts movement kinetics were also analysed, and several mathematical models were employed to ascertain the drug release mechanisms. The drug release markedly depends on the drug solubility and the carbohydrate nature but is practically not affected by the drying process and the initial matrix porosity. A faster drug release is observed for matrices containing diltiazem HCl compared with those containing anhydrous theophylline, in accordance with the higher drug solubility and the higher friability of diltiazem matrices. In fact, although diffusion is the prevailing drug release mechanism for all matrices, the erosion mechanism seems to have some contribution in several formulations containing diltiazem. A reduction in the surface exposed to the dissolution medium (radial release studies) leads to a decrease in the drug release rate, but the release mechanism is not essentially modified. The nearly constant erosion front movement confirms the behaviour of these systems as inert matrices where the drugs are released mainly by diffusion through the porous structure.

Pharmaceutical acrylic beads obtained by suspension polymerization containing cellulose nanowhiskers as excipient for drug delivery

Direct compression is one of the most popular techniques to prepare tablets but only a few commercial excipients are well adapted for this process into controlled release formulations. In the last years, the introduction of new materials for drug delivery matrix tablets has become more important. This paper evaluated the physicochemical and flow properties of new polymeric excipient of ethyl acrylate, methyl methacrylate and butyl metacrylate, synthesized by suspension polymerization using cellulose nanowhiskers as co-stabilizer, to be used as direct compression for modified release tablets. Infrared spectroscopy (FTIR) confirmed the success of the copolymerization reaction. Scanning electron microscopy (SEM) showed that excipient was obtained how spherical beads. Thermal properties of the beads were characterized by thermogravimetric (TG) analysis. Particle size analysis of the beads with cellulose nanowhiskers (CNWB) indicated that the presence of the nanowhiskers led to a reduction of particle size and to a narrower size distribution. In vitro test showed that the nanowhiskers and beads produced are nontoxic. Parameters such as Hausner ratio, Carr's index and cotangent of angle α were employed to characterize the flow properties of CNWB beads. Furthermore, the beads are used to produce tablets by direct compression contained propranolol hydrochloride as model drug. Dissolution tests performed suggested that beads could be used as excipient in matrix tablets with a potential use in drug controlled release.

Graft copolymers of ethyl methacrylate on waxy maize starch derivatives as novel excipients for matrix tablets: Physicochemical and technological characterisation

Nowadays, graft copolymers are being used as an interesting option when developing a direct compression excipient for controlled release matrix tablets. New graft copolymers of ethyl methacrylate (EMA) on waxy maize starch (MS) and hydroxypropylstarch (MHS) were synthesised by free radical polymerization and alternatively dried in a vacuum oven (OD) or freeze-dried (FD). This paper evaluates the performance of these new macromolecules and discusses the effect of the carbohydrate nature and drying process on their physicochemical and technological properties. Grafting of EMA on the carbohydrate backbone was confirmed by IR and NMR spectroscopy, and the grafting yields revealed that graft copolymers present mainly a hydrophobic character. The graft copolymerization also leads to more amorphous materials with larger particle size and lower apparent density and water content than carbohydrates (MS, MHS). All the products show a lack of flow, except MHSEMA derivatives. MSEMA copolymers underwent much plastic flow and less elastic recovery than MHSEMA copolymers. Concerning the effect of drying method, FD derivatives were characterised by higher plastic deformation and less elasticity than OD derivatives. Tablets obtained from graft copolymers showed higher crushing strength and disintegration time than tablets obtained from raw starches. This behaviour suggests that these copolymers could be used as excipients in matrix tablets obtained by direct compression and with a potential use in controlled release.

Poly( dl-lactic acid) as a direct compression excipient in controlled release tablets : Part I. Compaction behaviour and release characteristics of poly( dl-lactic acid) matrix tablets

High-molecular weight poly( dl-lactic acid) (PDLA, M v 85 000) was applied as a direct compression excipient in controlled release tablets. PDLA powders with good flowing properties were obtained by milling pre-cooled PDLA granules. Apparent yield pressure values ranged from 44 to 71 MPa for tabletting speeds of 0.033 and 300 mm/s, respectively, pointing to a high ductility and limited strain rate sensitivity. Tablets with good mechanical strength (tensile strength 2.5–3.7 MPa) were prepared at different compaction speeds. Dissolution experiments with different drugs showed that PDLA exhibited good sustained release properties. Initial tablet porosity, lubrication with magnesium stearate and pH of the dissolution medium hardly affected the release rate of the incorporated drug. Drug loads, however, markedly affected the release rate. For drug loads between 20 and 50% w/w, a constant fractional release rate was found. Upon further decreasing of the drug load, the release rate was found to increase. This remarkable finding was explained by the rapid and large increase of the pore volume of the tablets. The results show the unique properties of PDLA and its suitability to be applied as a direct compression and release controlling excipient in matrix tablets for oral drug administration.