Search Results (6)

In the present work, the application of lignin (LIG) as a bioactive additive for the preparation of drug-loaded tablets by direct compression has been studied, and its influence on the release of chlorzoxazone (CLZ) from the hydrophilic matrices has been followed. In hydrophilic matrices, the excipients Kollidon^® SR (KOL) and chitosan (CHT) have been used in various amounts and tested in the preparation of 500 mg tablets. They were used as matrix-forming agents, and their influence on the flow and the compressibility properties as well as their effect on the pharmaco-chemical characteristics of the matrix tablets have been studied. Based on the initial evaluation of the pharmaco-technical analysis, pharmaco-chemical characteristics, and in vitro release profile, three matrix tablet formulations (FLa, FLb, and FLc) were selected and further tested. They were evaluated through Fourier-transform infrared spectrometry (FTIR), X-ray diffraction (XRD), thermogravimetry (TG), differential scanning calorimetry (DSC), and in vitro dissolution tests. The three formulations were comparatively studied regarding the release kinetics of active substances using in vitro release testing. The in vitro kinetic study reveals a complex release mechanism occurring in two steps of drug release. The first one is a burst effect that occurs within the first 0–2 h, involving a rapid release of the majority of the drug in a short time, followed by the second step as a prolonged release of the drug, which is relatively constant with a fixed rate over the next 2–36 h. Two factors have been calculated to assess the release profile of chlorzoxazone: f1—the similarity factor and f2—the difference factor together with the correlation coefficient R². Comparing their values, the three optimal formulations have been selected, containing 55 mg LIG (FLa), 60 mg LIG (FLb), or 65 mg LIG (FLc), confirming that LIG next to KOL and CHT influenced the release characteristics of the matrix tablets. Due to the presence of lignin in the matrix of the three formulations, FLa, FLb, and FLc tablets with CLZ, the antioxidant activity has improved. The antioxidant activity of FLc was found to be 21.36% ± 1.06 greater than that of FLa and FLb. The tablets FLa, FLb, and FLc also presented higher antimicrobial activity against Staphylococcus aureus, Escherichia coli, Candida albicans, and colistin-resistant Klebsiella spp. The higher the concentration of LIG in the matrix (FLc), the higher the antimicrobial activity. By using LIG, the drug dose could be decreased. It can be concluded that lignin can be used as a multifunctional pharmaceutical bioactive additive/excipient for tablets. Its interesting properties have been proven, and its use as a pharmaceutical active additive should be exploited for different applications. Full article

This research work dives into the complexity of hot-melt extrusion (HME) and its influence on drug stability, focusing on solid dispersions containing 30% of glibenclamide and three 50:50 polymer blends. The polymers used in the study are Ethocel Standard 10 Premium, Kollidon SR and Affinisol HPMC HME 4M. Glibenclamide solid dispersions are characterized using thermal analyses (thermogravimetric analysis (TGA) and differential scanning calorimetry), X-ray diffraction and scanning electron microscopy. This study reveals the transformation of glibenclamide into impurity A during the HME process using mass spectrometry and TGA. Thus, it enables the quantification of the extent of degradation. Furthermore, this work shows how polymer–polymer blend matrices exert an impact on process parameters, the active pharmaceutical ingredient’s physical state, and drug release behavior. In vitro dissolution studies show that the polymeric matrices investigated provide extended drug release (over 24 h), mainly dictated by the polymer’s chemical nature. This paper highlights how glibenclamide is degraded during HME and how polymer selection crucially affects the sustained release dynamics. Full article

The modified release of active substances such as chlorzoxazone from matrix tablets, based on Kollidon^®SR and chitosan, depends both on the drug solubility in the dissolution medium and on the matrix composition. The aim of this study is to obtain some new oral matrix tablet formulations, based on Kollidon^®SR and chitosan, in order to optimize the low-dose oral bioavailability of chlorzoxazone, a non-steroidal anti-inflammatory drug of class II Biopharmaceutical Classification System. Nine types of chlorzoxazone matrix tablets were obtained using the direct compression method by varying the components ratio as 1:1, 1:2, and 1:3 chlorzoxazone/excipients, 20–40 w/w % Kollidon^®SR, 3–7 w/w % chitosan while the auxiliary substances: Aerosil^® 1 w/w %, magnesium stearate 0.5 w/w % and Avicel^® up to 100 w/w % were kept in constant concentrations. Pharmaco-technical characterization of the tablets included the analysis of flowability and compressibility properties (flow time, friction coefficient, angle of repose, Hausner ratio, and Carr index), and pharmaco-chemical characteristics (such as mass and dose uniformity, thickness, diameter, mechanical strength, friability, softening degree, and in vitro release profiles). Based on the obtained results, only three matrix tablet formulations (F1b, F2b, and F3b, containing 30 w/w % KOL and 5 w/w % CHT, were selected and further tested. These formulations were studied in detail by Fourier-transform infrared spectrometry, X-ray diffraction, thermogravimetry, and differential scanning calorimetry. The three formulations were comparatively studied regarding the release kinetics of active substances using in vitro release testing. The results were analyzed by fitting into four representative mathematical models for the modified-release oral formulations. In vitro kinetic study revealed a complex mechanism of release occurring in two steps of drug release, the first step (0–2 h) and the second (2–36 h). Two factors were calculated to assess the release profile of chlorzoxazone: f1—the similarity factor, and f2—the factor difference. The results have shown that both Kollidon^®SR and chitosan may be used as matrix-forming agents when combined with chlorzoxazone. The three formulations showed optima pharmaco-technical properties and in vitro kinetic behavior; therefore, they have tremendous potential to be used in oral pharmaceutical products for the controlled delivery of chlorzoxazone. In vitro dissolution tests revealed a faster drug release for the F2b sample. Full article

Hydroxypropyl methylcellulose (HPMC) is a preferred hydrophilic matrix former for controlled release formulations produced through continuous twin-screw wet granulation. However, a non-homogeneous API distribution over sieve fractions with underdosing in the fines fraction (<150 µm) was previously reported. This could result in content uniformity issues during downstream processing. Therefore, the current study investigated the root cause of the non-homogeneous theophylline distribution. The effect of process parameters (L/S-ratio and screw configuration) and formulation parameters (matrix former and filler type) on content uniformity was studied. Next, the influence of the formulation parameters on tableting and dissolution behavior was investigated. Altering the L/S-ratio or using a more aggressive screw configuration did not result in a homogeneous API distribution over the granule sieve fractions. Using microcrystalline cellulose (MCC) as filler improved the API distribution due to its similar behavior as HPMC. As excluding HPMC or including a hydrophobic matrix former (Kollidon SR) yielded granules with a homogeneous API distribution, HPMC was identified as the root cause of the non-homogeneous API distribution. This was linked to its fast hydration and swelling (irrespective of the HPMC grade) upon addition of the granulation liquid. Full article

The impact of hot-melt extrusion (HME) on the solid-state properties of four methacrylic (Eudragit^® L100-55, Eudragit^® EPO, Eudragit^® RSPO, Eudragit^® RLPO) and four polyvinyl (Kollidon^® VA64, Kollicoat^® IR, Kollidon^® SR, and Soluplus^®) polymers was studied. Overall, HME decreased Tg but increased electrostatic charge and surface free energy. Packing density decreased with electrostatic charge, whereas Carr’s and Hausner indices showed a peak curve dependency. Overall, HME reduced work of compaction (Wc), deformability (expressed as Heckel P_Y and Kawakita 1/b model parameters and as slope S′ of derivative force/displacement curve), and tablet strength (TS) but increased elastic recovery (ER). TS showed a better correlation with S′ than P_Y and 1/b. Principal component analysis (PCA) organized the data of neat and extruded polymers into three principal components explaining 72.45% of the variance. The first included Wc, S′ and TS with positive loadings expressing compaction, and ER with negative loading opposing compaction; the second included P_Y, 1/b, and surface free energy expressing interactivity with positive loadings opposing tap density or close packing. Hierarchical cluster analysis (HCA) assembled polymers of similar solid-state properties regardless of HME treatment into a major cluster with rescaled distance Cluster Combine Index (CCI) < 5 and several other weaker clusters. Polymers in the major cluster were: neat and extruded Eudragit^® RSPO, Kollicoat^® IR, Kollidon^® SR, Soluplus^®, and extruded Eudragit^® L100-55. It is suggested that PCA may be used to distinguish variables having similar or dissimilar activity, whereas HCA can be used to cluster polymers based on solid-state properties and pick exchangeable ones (e.g., for sustain release or dissolution improvement) when the need arises. Full article

Regarding compliance and minimization of side effects of nilotinib therapy, there is a medical need to have a gastroretentive drug delivery system (GRDDS) to enhance the oral bioavailability that is able to administer an optimal dose in a quaque die (QD) or daily manner. In this study, the influence on a swelling and floating (sf) GRDDS composed of a polymeric excipient (HPMC 90SH 100K, HEC 250HHX, or PEO 7000K) and Kollidon^® SR was examined. Results demonstrated that PEO 7000K/Kollidon SR (P/K) at a 7/3 ratio was determined to be a basic GRDDS formulation with optimal swelling and floating abilities. MCC PH102 or HPC_sssl,SFP was further added at a 50% content to this basic formulation to increase the tablet hardness and release all of the drug within 24 h. Also, the caplet form and capsule form containing the same formulation demonstrated higher hardness for the former and enhanced floating ability for the latter. A pharmacokinetic study on rabbits with pH values in stomach and intestine similar to human confirmed that the enhanced oral bioavailability ranged from 2.65–8.39-fold with respect to Tasigna, a commercially available form of nilotinib. In conclusion, the multiple of enhancement of the oral bioavailability of nilotinib with sfGRDDS could offer a pharmacokinetic profile with therapeutic effectiveness for the QD administration of a reasonable dose of nilotinib, thereby increasing compliance and minimizing side effects. Full article