Modulation of the Release of a Non-Interacting Low Solubility Drug from Chitosan Pellets Using Different Pellet Size, Composition and Numerical Optimization

Abstract

Two size classes of piroxicam (PXC) pellets (mini (380–550 μm) and conventional (700–1200 μm)) were prepared using extrusion/spheronization and medium viscosity chitosan (CHS). Mixture experimental design and numerical optimization were applied to distinguish formulations producing high sphericity pellets with fast or extended release. High CHS content required greater wetting liquid volume for pellet formation and the diameter decreased linearly with volume. Sphericity increased with CHS for low-to-medium drug content. Application of PXRD showed that the drug was a mixture of form II and I. Crystallinity decreased due to processing and was significant at 5% drug content. Raman spectroscopy showed no interactions. At pH 1.2, the dissolved CHS increased ‘apparent’ drug solubility up to 0.24 mg/mL while, at pH 5.6, the suspended CHS increased ‘apparent’ solubility to 0.16 mg/mL. Release at pH 1.2 was fast for formulations with intermediate CHS and drug levels. At pH 5.6, conventional pellets showed incomplete release while mini pellets with a CHS/drug ratio ≥2 and up to 21.25% drug, showed an extended release that was completed within 8 h. Numerical optimization provided optimal formulations for fast release at pH 1.2 with drug levels up to 40% as well as for extended release formulations with drug levels of 5% and 10%. The Weibull model described the release kinetics indicating complex or combined release (parameter ‘b’ > 0.75) for release at pH 1.2, and normal diffusion for the mini pellets at pH 5.6 (‘b’ from 0.63 to 0.73). The above results were attributed mainly to the different pellet sizes and the extensive dissolution/erosion of the gel matrix was observed at pH 1.2 but not at pH 5.6.

Co-Spray Drying of Paracetamol and Propyphenazone with Polymeric Binders for Enabling Compaction and Stability Improvement in a Combination Tablet

“…The drug release data were described using the Weibull equation (Equation (6)) [ 25 , 26 ]. It distinguishes drug release mechanisms, which in the present work is very likely due to the different release characteristics of HPMC and HPC tablets [ 27 ].…”

Application of Multiple Linear Regression and Artificial Neural Networks for the Prediction of the Packing and Capsule Filling Performance of Coated and Plain Pellets Differing in Density and Size

“…The consumed quantities of binder/gram solids for the MCC/PCT mixtures were between 4.8 and 17.6 mL, for the MCC/CPH between 7.2 and 18.4 mL, and for the MCC/BSF between 5.4 and 18.5 mL. The wet mass was immediately transferred into a spheronizer (Model 120, Caleva) fitted with a cross-hatch plate and rotated for 10 min, with the small pellets at 940 rpm corresponding to a linear velocity of 5.92 m/s and the large pellets at 1440 rpm corresponding to a linear velocity of 9.07 m/s [9]. MCC/modifier pellets with different proportions, 10% to 80%, were prepared and different density ranges were obtained.…”

“…The obtained p app ranges were: 1.34-1.68 g/cc for MCC/PCT, 1.68-2.89 g/cc for MCC/CPH, and 1.68-4.68 g/cc for MCC/BSF. The two lines in each subfigure correspond to the experimental or "apparent" (solid symbols) and to the theoretical pellet densities, calculated from those of the primary components (for MCC 1.682 g/cc, for PCT 1.343, for CPH 2.893, and for BSF 4.675 g/cc) using Equation (9).…”

“…Design of experiments (DoE), supplemented with polynomial model fitting via multiple linear regression (MLR), is gaining acceptance as a prediction tool in pharmaceutical formulation work due to its simplicity, software availability, and the physical interpretation of the effects and interactions [8,9]. However, there are cases where high precision levels in conjunction with generalizing ability are required and MLR may not adequately satisfy these requirements [10].…”

Functional Polymers for Controlled Drug Release

“…Intelligent polymeric devices able to undergo morphological modifications in response to an internal or external stimulus, such as pH, redox balance, temperature, magnetic field, and light have been actively pursued [8][9][10]. In particular, in this Special Issue, Partheniadis et al [11] synthesized pharmaceutical pellets [12] of different sizes, using an extrusion/spheronization technique, and medium viscosity chitosan for the pH-dependent delivery of piroxicam. The authors suggested that a remarkable reduction in pellet size influenced the release rate, avoiding the need to employ hydrophilic excipients such as lactose [13].…”