Search Results (5)

The application of mesoporous carriers in formulations of amorphous solid dispersions (ASDs) has been suggested to enhance the stability of amorphous drugs. However, mesoporous carriers do not demonstrate satisfactory inhibitory effects on the precipitation of active pharmaceutical ingredients (APIs), and the inclusion of an appropriate polymer within ASDs becomes imperative to maintaining drug supersaturation. The aim of this study was to evaluate ternary olanzapine (OLN) ASDs with Syloid 244FP and to find an appropriate polymeric carrier. The polymer’s selection criteria were based on the physical stability of the ASDs and the release rate of the drug from the systems. The polymers investigated were hydroxypropylmethyl cellulose (HPMC) and copovidone (coPVP). The formation of ASDs was achievable in all investigated cases, as demonstrated by the complete lack of crystallinity confirmed through both powder X-ray diffraction (pXRD) analysis and differential scanning calorimetry (DSC) for all developed formulations. The solvent shift method was employed to evaluate the ability of the studied carriers to inhibit the precipitation of supersaturated OLN. coPVP emerged as a more suitable precipitation inhibitor compared with HPMC and Syloid 244 FP. Subsequently, in vitro dissolution studies under non-sink conditions revealed a higher degree of supersaturation in ternary systems where coPVP was used as a polymeric carrier, as these systems exhibited, under the examined conditions, up to a 2-fold increase in the released OLN compared with the pure crystalline drug. Moreover, stability studies conducted utilizing pXRD demonstrated that ternary formulations incorporating coPVP and Syloid 244 FP maintained stability for an extended period of 8 months. In contrast, binary systems exhibited a comparatively shorter stability duration, indicating the synergistic effect of coPVP and Syloid 244 FP on the physical stability of the amorphous API. Attenuated total reflectance–Fourier transform infrared (ATR-FTIR) studies showed that the development of stronger molecular interactions can be provided as an explanation for this synergistic effect, as the formation of robust H-bonds may be considered responsible for inhibiting the precipitation of the supersaturated API. Therefore, the incorporation of coPVP into OLN ASDs with Syloid 244 FP is considered a highly promising technique for increasing the degree of OLN supersaturation in in vitro dissolution studies and improving the stability of systems. Full article

The direct tailoring of the size, composition, or number of layers belongs to the advantages of 3D printing employment in producing orodispersible films (ODFs) compared to the frequently utilized solvent casting method. This study aimed to produce porous ODFs as a substrate for medicated ink deposited by a 2D printer. The innovative semi-solid extrusion 3D printing method was employed to produce multilayered ODFs, where the bottom layer assures the mechanical properties. In contrast, the top layer provides a porous structure for ink entrapment. Hydroxypropyl methylcellulose and polyvinyl alcohol were utilized as film-forming polymers, glycerol as a plasticizer, and sodium starch glycolate as a disintegrant in the bottom matrix. Several porogen agents (Aeroperl^® 300, Fujisil^®, Syloid^® 244 FP, Syloid^® XDP 3050, Neusilin^® S2, Neusilin^® US2, and Neusilin^® UFL2) acted as porosity enhancers in the two types of top layer. ODFs with satisfactory disintegration time were prepared. The correlation between the porogen content and the mechanical properties was proved. A porous ODF structure was detected in most samples and linked to the porogen content. SSE 3D printing represents a promising preparation method for the production of porous ODFs as substrates for subsequent drug deposition by 2D printing, avoiding the difficulties arising in casting or printing medicated ODFs directly. Full article

An automated compounding device can be a useful tool for the rapid and accurate production of small batches for personalized medicine as well as for clinical batches. A novel electronic liquid dispensing system (ELDS) was investigated to produce hard capsules with individualized dose strengths. An ethanol-based solvent system containing the antihypertensive enalapril maleate was extruded through a cannula into prefilled capsules. The capsules were prefilled with a powder bed of mesoporous silica (Syloid 244 FP) or synthetic dibasic calcium phosphate anhydrous (Fujicalin). The dosing accuracy as well as content uniformity of ELDS was compared with manual preparation using a Hamilton syringe (HS). Both methods met the pharmacopeia criteria for all formulations with an acceptance value (AV) less than 15. Drug adherence to the capsule shells was also investigated. A recovery rate of 98% of enalapril maleate showed almost no drug loss, but the appropriateness of the new dispensing method. Full article

Background: Intestinal nematode infections are usually treated with benzimidazole drugs, but the emergence of resistance to these drugs has led to an increasing demand of new anthelmintic strategies. A new microemulsion formulation (ME) consisting of an Artemisia absinthium extract with proven nematocidal efficacy was previously developed. The aim of our study is to implement a D-optimal mixture design methodology to increase the amount of a silica material (loaded with this ME) in a tablet formulation, considering its tensile strength and disintegration time. Methods: 16 experiments or combinations of the 6 tablet components (loaded silica, microcrystalline cellulose, polyvinylpyrrolidone, croscarmellose, Syloid^® 244 FP and magnesium stearate) were assessed. Tensile strength and disintegration time models were developed, and an optimization process was carried out. Results: Tensile strength was improved by increasing the polyvinylpyrrolidone content, while croscarmellose decreased the disintegration time. The optimized powder mixture contains 49.7% w/w of the loaded silica material. A compression force of 12 kN was applied to the powder mixture to form tablets with a tensile strength of 2.0 MPa and a disintegration time of 3.8 min. Conclusions: Our results show that D-optimal mixture designs provide a promising approach to formulate liquid-loaded silica materials. Full article

In this paper, the role of mesoporous silica (MS) particle size in the stabilization of amorphous simvastatin (SVT) is revealed. For inhibiting recrystallization of the supercooled drug, the two MS materials (Syloid^® XDP 3050 and Syloid^® 244 FP) were employed. The crystallization tendency of SVT alone and in mixture with the MS materials was investigated by Differential Scanning Calorimetry (DSC) and Broadband Dielectric Spectroscopy (BDS). Neither confinement of the SVT molecules inside the MS pores nor molecular interactions between functional groups of the SVT molecules and the surface of the stabilizing excipient could explain the observed stabilization effect. The stabilization effect might be correlated with diffusion length of the SVT molecules in the MS materials that depended on the particle size. Moreover, MS materials possessing different particle sizes could offer free spaces with different sizes, which might influence crystal growth of SVT. All of these factors must be considered when mesoporous materials are used for stabilizing pharmaceutical glasses. Full article