Evaluation of Experimental Multi-Particulate Polymer-Coated Drug Delivery Systems with Meloxicam
Download the full article here: Evaluation of Experimental Multi-Particulate Polymer-Coated Drug Delivery Systems with Meloxicam
or continue reading here: Hîrjău, M.; Miron, D.S.; Anuța, V.; Lupuliasa, D.; Ghica, M.V.; Jinga, V.; Dinu-Pîrvu, C.-E. Evaluation of Experimental Multi-Particulate Polymer-Coated Drug Delivery Systems with Meloxicam. Coatings 2020, 10, 490.
Introduction
Pharmaceutical pellets are small, spherical, free-flowing, and high-density granules, with size ranging from 0.1 to 1.5 mm. When an active pharmaceutical ingredient is formulated into these multi-particulate drug delivery systems, the total dose is divided into the subunits represented by the pellets. For various pharmaceutical applications, drug-loaded pellets can be coated with polymeric films and subsequently filled into hard capsules or compressed into multiple unit pellet systems (MUPS).
These multi-particulate drug delivery systems display a number of technological and clinical advantages, compared to single-unit dosage forms (with conventional or modified release), such as simplicity of coating, lower intra- and inter-subject variability of drug plasma levels, stable plasma concentrations and reduced bowel irritations, due to the uniform distribution of the pellets in the gastrointestinal tract. Furthermore, pellets are less susceptible to allow a sudden and complete release of the drug (dose dumping effect), as each pellet acts as an individual drug reservoir.
Extrusion-spheronization is one of the most employed pelletization techniques . This might be attributed to the fact that by using this method, product quality is controlled mainly by the formulation factors, while technological parameters (machine settings) are less critical. Microcrystalline cellulose (MCC) is usually the main excipient used for the pellet base , acting as a spheronization aid due to its ability to retain large amounts of water in its structure, providing an elasto-plastic wet mass that is suitable for successful extrusion and good product quality.
Pellets can be coated with polymeric coatings, in order to mask the unpleasant taste of certain active pharmaceutical ingredients (APIs), to improve their stability, to avoid interactions between other formulation components and the drug, but, more often, in order to achieve a target release profile for the drug.
In the formulation of advanced drug delivery systems, functional coatings which lead to an extended or delayed release of the drug are often employed.
Such films allow formulators to control the rate of drug release as a function of time (in the case of modified release coatings) or a response to the environment (e.g., depending on the pH, in the case of enteric coatings). Enteric-coated pellets are particularly suitable for the administration of drugs that are unstable in the gastric fluid or those that cause the irritation of the gastric mucosa or that are absorbed at the duodenal or intestinal level .
Application of functional coating can be performed by using various techniques such as powder layering or spray coating of suspension containing dissolved polymer.
Meloxicam (MX) is a preferential inhibitor of cyclooxygenase 2 (COX-2) non-steroidal, anti-inflammatory, anti-rheumatoid, and analgesic drug, belonging to the oxicam class. Its oral formulations are widely used to treat rheumatoid arthritis, ankylosing spondylitis, as well as other various pain syndromes of skeletomuscular origin.
According to the Biopharmaceutical Classification System (BCS), it is included in Class II because of its low, pH dependent solubility but good permeability. Its low water solubility (12 µg/mL) and wettability lead to poor drug dissolution and consequently variations in bioavailability.
As other NSAIDs, meloxicam has some significant side-effects, causing potentially serious dose-dependent gastrointestinal (GI) complications such as upper GI bleeding. Therefore, there is a considerable interest in developing new forms to prevent its delivery in the gastric compartment and allow its release at the proximal intestinal lumen, preventing therefore the gastric lesions resulting from the direct contact with the gastric mucosa. Thus, it would seem plausible that the formulation of meloxicam as enteric release pellets would overcome some of these disadvantages by avoiding gastrointestinal adverse reactions.
Also, pursuing an extended release profile would result in the maintenance of therapeutic plasma concentrations over longer periods of time, which would ultimately provide a safer and more convenient dosing schedule for the patient. Thus, an orally administered extended-release meloxicam formulation provided therapeutic levels of the drug for durations ranging from 48 to 72 h, that would make meloxicam an ideal candidate for administration for chronic pain management. A similar approach was considered by Auriemma G. et al. who have developed floating gastro-retentive gel-beads with sustained release properties containing piroxicam in order to overcome fluctuations in plasma levels.
The aim of the present study is to design and develop a polymer-coated modified release multiunit dosage form containing meloxicam able to provide an extended release of the drug, while reducing to a minimum the potential upper GI side effects of the drug due to its direct contact with the gastric mucosa.
For the experimental dosage forms we aim to also investigate the correlations between the film surface characteristics and the in vitro drug dissolution profile. The film properties that were assessed were the morphology of the surface and cross-section of coating pellets.
Read more on Talc as a pharmaceutical excipient here: