ABSTRACT
The formulation and the coating composition of biopolymeric pellets containing ranolazine were studied to improve their technological and biopharmaceutical properties. Eudragit L100 (EU L100) and Eudragit L30 D-55-coated alginate and alginate-hydroxypropylcellulose (HPC) pellets were prepared by ionotropic gelation using 3 concentrations of HPC (0.50%, 0.65%, and 1.00% wt/wt) and applying different percentages (5%, 10%, 20%, and 30% wt/wt) of coating material. The uncoated pellets were regular in shape and had mean diameter between 1490 and 1570 µm. The rate and the entity of the swelling process were affected by the polymeric composition: increasing the HPC concentration, the structure of the pellets became more compact and slowed down the penetration of fluids. Coated alginate-HPC formulations were able to control the drug release at neutral pH: a higher quantity of HPC in the system determined a slower release of the drug. The nature of the coating polymer and the coating level applied affected the drug release in acidic environment: EU L100 gave better performance than Eudragit L30 D-55 and the best coating level was 20%. The pellets containing 0.65% of HPC and coated with 20% EU L100 represented the best formulation, able to limit the drug release in acidic environment and to control it at pH 6.8.
Subject(s)
Alginates/chemistry , Cellulose/analogs & derivatives , Chemistry, Pharmaceutical/methods , Drug Implants/chemistry , Ranolazine/chemistry , Alginates/pharmacokinetics , Cardiovascular Agents/chemistry , Cardiovascular Agents/pharmacokinetics , Cellulose/chemistry , Cellulose/pharmacokinetics , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , Drug Compounding , Drug Implants/pharmacokinetics , Drug Liberation , Glucuronic Acid/chemistry , Glucuronic Acid/pharmacokinetics , Hexuronic Acids/chemistry , Hexuronic Acids/pharmacokinetics , Methacrylates/chemistry , Methacrylates/pharmacokinetics , Polymers/chemistry , Polymers/pharmacokinetics , Polymethacrylic Acids/chemistry , Polymethacrylic Acids/pharmacokinetics , Ranolazine/pharmacokineticsABSTRACT
In this work alginate and alginate-chitosan beads containing celecoxib solubilized into a self-emulsifying phase were developed in order to obtain a drug delivery system for oral administration, able to delay the drug release in acidic environment and to promote it in the intestinal compartment. The rationale of this work was linked to the desire to improve celecoxib therapeutic effectiveness reducing its gastric adverse effects and to favor its use in the prophylaxis of colon cancer and as adjuvant in the therapy of familial polyposis. The systems were prepared by ionotropic gelation using needles with different diameters (400 and 600 µm). Morphology, particle size, swelling behavior, and in vitro drug release performance of the beads in aqueous media with different pH were investigated. The experimental results demonstrated that the presence of chitosan in the formulation caused an increase of the mechanical resistance of the bead structure and, as a consequence, a limitation of the bead swelling ability and a decrease of the drug release rate at neutral pH. Alginate-chitosan beads could be a good tool to guarantee a celecoxib colon delivery.
ABSTRACT
In this work, alginate, alginate-pectin and alginate-hydroxypropylcellulose pellets were produced by ionotropic gelation and characterized. Ibuprofen was selected as model drug; it was suspended in the polymeric solution in crystalline form or dissolved in a self-emulsifying phase and then dispersed into the polymeric solution. The self-emulsifying excipient platform composed of Labrasol (PEG-8 caprylic/capric glycerides) and d-α-tocopherol polyethylene glycol 1000 succinate (TPGS), able to solubilize the drug was used to improve the technological and biopharmaceutical properties of the alginate pellets. The pellets had diameters between 1317 and 2026 µm and a high drug content (>51%). DSC analysis showed the amorphous state of drug in the pellets containing the self-emulsifying phase. All the systems restricted drug release in conditions simulating the gastric environment and made the drug completely available at a pH value typical for the intestine. Only alginate-HPC systems containing the drug solubilized into the self-emulsifying phase showed the ability to partially control the release of ibuprofen at neutral pH. The self-emulsifying excipient platform is a useful tool to improve technological and biopharmaceutical properties of alginate-HPC pellets.
Subject(s)
Alginates/chemistry , Cellulose/analogs & derivatives , Excipients/chemistry , Ibuprofen/administration & dosage , Calorimetry, Differential Scanning , Cellulose/chemistry , Chemistry, Pharmaceutical/methods , Crystallization , Drug Liberation , Emulsions , Glucuronic Acid/chemistry , Glycerides/chemistry , Hexuronic Acids/chemistry , Hydrogen-Ion Concentration , Ibuprofen/chemistry , Particle Size , Pectins/chemistry , Polyethylene Glycols/chemistry , Solubility , Technology, Pharmaceutical/methods , Vitamin E/analogs & derivatives , Vitamin E/chemistryABSTRACT
The aim of the work was to realize itraconazole-loaded formulations in form of microparticles using a fast, simple and solvent free production procedure. The selected excipients were able to enhance wettability of the final product, to increase drug dissolution rate and to maintain drug in solution thanks to the formation of an emulsified system after contact with the gastrointestinal fluids. Itraconazole formulations contained a structuring lipid, a solubilizing agent and a surface active substance and were prepared by a hot melt method (MMS, melting-milling-sieving). The characterization included drug content determination, granulometric distribution, differential scanning calorimetry (DSC) and in vitro drug release test, physical and technological stability after 12 months of ambient condition storage. The formulations were composed of particles with diameter lower than 355 µm. DSC analysis evidenced that itraconazole was almost completely in the amorphous form; the results of the in vitro drug release tests showed that these formulations were able to increase the rate of the drug release compared to that of the free drug. Stability data showed no significant changes in the thermal and release profiles, confirming that the selected excipients protected the drug avoiding its conversion from amorphous state into crystalline form and maintaining unchanged the delivery behavior.
Subject(s)
Itraconazole/chemistry , Technology, Pharmaceutical/methods , Calorimetry, Differential Scanning , Crystallization , Drug Compounding , Drug Liberation , Drug Stability , Drug Storage , Excipients/chemistry , Particle Size , Solubility , Surface PropertiesABSTRACT
VarioSol® is an innovative, solvent-free technology able to produce microparticles exploiting near-critical CO(2) properties as spraying and cooling agent. The aim of the present work was to evaluate the feasibility to produce in a single processing step by VarioSol® technology, oral ketoprofen-loaded microparticles with gastro-protective properties. The obtained products were powders composed of regular in shape and small in diameter microparticles, characterized by high drug content (40%) and good flow properties. Microparticles were composed by anionic lipids scarcely soluble at acidic pH, blended with gastro-resistant polymers of the methacrylate type. In vitro drug release results indicated that the drug was rapidly delivered from the microparticulate systems in phosphate buffer at pH 6.8, while in acidic medium, the microparticles were able to retard the drug release process but without reaching complete gastro-resistance. However, the results obtained in this study, although non optimal, are not far from the specifications required for gastro-resistant release products (i.e., no more than 10% drug released after 1h at pH 1.0) according to EMA guidelines and represent a good starting point for future formulation development.
