Evaluation of the Release Kinetics of a Pharmacologically Active Substance from Model Intra-Articular Implants Replacing the Cruciate Ligaments of the Knee
Abstract:Implants are readily applied as a convenient method of therapy. There is great interest in the prolonged release of active substances from implants. The objective of this work was to evaluate the dissolution kinetics of steroidal anti-inflammatory preparation (SAP) released from novel implants, and to test the influence of the technology on SAP release kinetics. The proposed long-acting preparations may overcome difficulties resulting from repeated injections and often visits to ambulatory clinic, as the stabi… Show more
“…The dissolution profiles of all the tablets were curve-fitted to mathematical drug release models ( Table 5 ). The HPMC-AS HG release profiles fit well with the Higuchi model, whereas there is a declining trend of correlation to the Higuchi model observed in HPMC-AS MG and HPMC-AS LG which is understandable since the Higuchi model considers dissolution, as well as shape change of the system insignificant and, is more focused on the release via diffusion [ 49 ].…”
Section: Resultsmentioning
confidence: 94%
“…It can be seen that all the profiles fit well with the zero-order release kinetics ( Table 5 ). This is because the drug release is not due to the immediate disaggregation of the dosage form as seen in immediate release or orally disintegrating tablets, but rather due to the slow release of the drug [ 49 ]. This slow-release can be attributed to the sink conditions maintained throughout the study and the inherent properties of ASDs where the drug releases occur by slow surface dissolution of the tablets.…”
This research demonstrates the use of fill density as an effective tool for controlling the drug release without changing the formulation composition. The merger of hot-melt extrusion (HME) with fused deposition modeling (FDM)-based 3-dimensional (3-D) printing processes over the last decade has directed pharmaceutical research towards the possibility of printing personalized medication. One key aspect of printing patient-specific dosage forms is controlling the release dynamics based on the patient’s needs. The purpose of this research was to understand the impact of fill density and interrelate it with the release of a poorly water-soluble, weakly acidic, active pharmaceutical ingredient (API) from a hydroxypropyl methylcellulose acetate succinate (HPMC-AS) matrix, both mathematically and experimentally. Amorphous solid dispersions (ASDs) of ibuprofen with three grades of AquaSolveTM HPMC-AS (HG, MG, and LG) were developed using an HME process and evaluated using solid-state characterization techniques. Differential scanning calorimetry (DSC), powder X-ray diffraction (pXRD), and polarized light microscopy (PLM) confirmed the amorphous state of the drug in both polymeric filaments and 3D printed tablets. The suitability of the manufactured filaments for FDM processes was investigated using texture analysis (TA) which showed robust mechanical properties of the developed filament compositions. Using FDM, tablets with different fill densities (20–80%) and identical dimensions were printed for each polymer. In vitro pH shift dissolution studies revealed that the fill density has a significant impact (F(11, 24) = 15,271.147, p < 0.0001) and a strong negative correlation (r > −0.99; p < 0.0001) with the release performance, where 20% infill demonstrated the fastest and most complete release, whereas 80% infill depicted a more controlled release. The results obtained from this research can be used to develop a robust formulation strategy to control the drug release from 3D printed dosage forms as a function of fill density.
“…The dissolution profiles of all the tablets were curve-fitted to mathematical drug release models ( Table 5 ). The HPMC-AS HG release profiles fit well with the Higuchi model, whereas there is a declining trend of correlation to the Higuchi model observed in HPMC-AS MG and HPMC-AS LG which is understandable since the Higuchi model considers dissolution, as well as shape change of the system insignificant and, is more focused on the release via diffusion [ 49 ].…”
Section: Resultsmentioning
confidence: 94%
“…It can be seen that all the profiles fit well with the zero-order release kinetics ( Table 5 ). This is because the drug release is not due to the immediate disaggregation of the dosage form as seen in immediate release or orally disintegrating tablets, but rather due to the slow release of the drug [ 49 ]. This slow-release can be attributed to the sink conditions maintained throughout the study and the inherent properties of ASDs where the drug releases occur by slow surface dissolution of the tablets.…”
This research demonstrates the use of fill density as an effective tool for controlling the drug release without changing the formulation composition. The merger of hot-melt extrusion (HME) with fused deposition modeling (FDM)-based 3-dimensional (3-D) printing processes over the last decade has directed pharmaceutical research towards the possibility of printing personalized medication. One key aspect of printing patient-specific dosage forms is controlling the release dynamics based on the patient’s needs. The purpose of this research was to understand the impact of fill density and interrelate it with the release of a poorly water-soluble, weakly acidic, active pharmaceutical ingredient (API) from a hydroxypropyl methylcellulose acetate succinate (HPMC-AS) matrix, both mathematically and experimentally. Amorphous solid dispersions (ASDs) of ibuprofen with three grades of AquaSolveTM HPMC-AS (HG, MG, and LG) were developed using an HME process and evaluated using solid-state characterization techniques. Differential scanning calorimetry (DSC), powder X-ray diffraction (pXRD), and polarized light microscopy (PLM) confirmed the amorphous state of the drug in both polymeric filaments and 3D printed tablets. The suitability of the manufactured filaments for FDM processes was investigated using texture analysis (TA) which showed robust mechanical properties of the developed filament compositions. Using FDM, tablets with different fill densities (20–80%) and identical dimensions were printed for each polymer. In vitro pH shift dissolution studies revealed that the fill density has a significant impact (F(11, 24) = 15,271.147, p < 0.0001) and a strong negative correlation (r > −0.99; p < 0.0001) with the release performance, where 20% infill demonstrated the fastest and most complete release, whereas 80% infill depicted a more controlled release. The results obtained from this research can be used to develop a robust formulation strategy to control the drug release from 3D printed dosage forms as a function of fill density.
“…The Korsmeyer-Peppas model was used to further explain the mechanism of curcumin release. The release was found to follow Fickian diffusion as the release exponent was 0.3 (<0.5) [18]. This means that curcumin diffused at a comparatively slower rate, as the diffusion time was longer based on the square root kinetic of the Korsmeyer-Peppas model.…”
Curcumin nanoemulsion was prepared using coconut oil, Tween 80 (surfactant) and polyethylene glycol (co-solvent) with the addition of honey and glycerol as additives. The nanoemulsion was optimized and systematically characterized for transdermal delivery. Small particle size (15.92 nm), low polydispersity index (0.17) and slight acidic (pH 4.18) curcumin nanoemulsion was obtained without any chemical degradation based on the Fourier transform infrared (FTIR) spectrum. The incorporation of curcumin inside nanoglobul improved curcumin stability and skin permeability. Its high permeability can be seen from Nile dyed curcumin in different layers of skin through fluorescent imaging. The release kinetic of curcumin followed the Higuchi model, which explains why the skin permeation was a Fickian diffusion-controlled process because the Korsmeyer constant was proven to be 0.3 (<0.5). Nanoencapsulation slightly decreased the antioxidant capacity of curcumin for about 7.9% compared to its free counterpart. It showed low cytotoxicity (EC50 2.3552 µg/mL) to human skin fibroblasts. Cell death was noticed at a high concentration (2.5 µg/mL) of treatment. Curcumin was also found to promote wound closure at low concentration 0.1563 µg/mL and was comparable with the performance of ascorbic acid based on scratch assay. Therefore, this nutritious curcumin nanoemulsion is a promising transdermal delivery system for topical application.
“…Mathematical models represent a fundamental tool to optimally design new pharmaceutical systems, to study drug formulations and to evaluate in vitro and in vivo releases [23][24][25][26]. They rely on the model fitting of experimental data and equations and they enable a quantitative interpretation of the values obtained from a drug release assay [27].…”
In recent years, drug delivery systems have become some of the main topics within the biomedical field. In this scenario, polymeric microparticles (MPs) are often used as carriers to improve drug stability and drug pharmacokinetics in agreement with this kind of treatment. To avoid a mere and time-consuming empirical approach for the optimization of the pharmacokinetics of an MP-based formulation, here, we propose a simple predictive in silico-supported approach. As an example, in this study, we report the ability to predict and tune the release of curcumin (CUR), used as a model drug, from a designed combination of different poly(d,l-lactide-co-glycolide) (PLGA) MPs kinds. In detail, all CUR–PLGA MPs were synthesized by double emulsion technique and their chemical–physical properties were characterized by Mastersizer and scanning electron microscopy (SEM). Moreover, for all the MPs, CUR encapsulation efficiency and kinetic release were investigated through the UV–vis spectroscopy. This approach, based on the combination of in silico and experimental methods, could be a promising platform in several biomedical applications such as vaccinations, cancer-treatment, diabetes therapy and so on.
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