Pemilihan Jenis Koformer dan Metode Preparasi dalam Sistem Penghantaran Sediaan Ko-Amorf

Ko-amorf adalah suatu sistem multikomponen padat yang mengandung zat aktif dan molekul dengan berat molekul rendah lainnya (koformer) yang dapat berupa eksipien atau zat aktif yang relevan secara farmakologis. Formulasi ko-amorf yang dibuat dengan metode preparasi dan jenis koformer yang berbeda dapat menghasilkan perbedaan yang signifikan dalam stabilitas fisik dan profil disolusi suatu bentuk ko-amorf. Tujuan penulisan dari artikel review ini adalah untuk menggali informasi lebih dalam tentang sistem ko-amorf, klasifikasi ko-amorf, karakterisasi ko-amorf serta pengaruh jenis koformer dan metode preparasi ko-amorf terhadap pembentukan ko-amorf. Artikel review ini disusun dengan literature search melalui PubMed, MDPI dan Science Direct dengan memasukkan kata kunci co-amorphous, co-amorphous formulations, co-amorphous stabilizers, co-amorphous drug formulations. Dari review ini ditemukan terdapat beberapa jenis koformer yang dapat digunakan untuk pembentukan ko-amorf yaitu dapat berupa zat aktif yang relevan secara farmakologis dan eksipien seperti diantaranya yaitu asam amino, asam karboksilat, asam tanat, quercetin, sakarin dan nikotinamid. Dan untuk metode preparasi ko-amorf yang dapat digunakan diantaranya yaitu ball milling, cryomilling, melt quenching/ quench cooling, hot melt extrusion, solvent evaporation, spray drying, freeze drying hingga teknologi seperti supercritical antisolvent dan microwave technique. Keberhasilan pembentukan ko-amorf ditentukan diantaranya oleh pemilihan jenis koformer yang melibatkan berbagai sifat yang perlu dipertimbangkan, seperti Tg, potensial ikatan hidrogen, ketercampuran/ miscibility, atau perilaku kristalisasi. Sifat zat aktif dan eksipien seperti stabilitas termal, suhu leleh dan kecenderungan kristalisasi zat aktif dan eksipien, menjadi faktor yang perlu diperhatikan dalam pemilihan metode preparasi ko-amorf.

Drug Amorphous Solid Dispersions Based on Poly(vinyl Alcohol): Evaluating the Effect of Poly(propylene Succinate) as Plasticizer

Although significant actions have been taken towards the utilization of poly(vinyl alcohol) (PVA) in the preparation of drug amorphous solid dispersions (ASDs) using fusion-based techniques (such as melt-quench cooling and hot-melt extrusion), several drawbacks regarding its rather high melting temperature and its thermal degradation profile make the use of the polymer extremely challenging. This is especially important when the active pharmaceutical ingredient (API) has a lower melting temperature (than PVA) or when it is thermally labile. In this vein, a previous study showed that newly synthesized polyester-based plasticizers may improve the processability and the thermal properties of PVA. However, the effects of such polyester-based plasticizers on the drug’s physicochemical and pharmaco-technical properties are yet unknown. Hence, the aim of the present study is to extend our previous findings and evaluate the use of poly(propylene succinate) (PPSu, i.e., the most promising plasticizer in regard to PVA) in the preparation of drug-loaded PVA-based ASDs. Dronedarone (DRN), a poorly water-soluble API, was selected as a model drug, and drug ASDs (using either neat PVA or PVA-PPSu) were prepared using the melt-mixing/quench cooling approach at low melting temperatures (i.e., 170 °C). DSC and pXRD analysis showed that a portion of the API remained crystalline in the ASDs prepared only with the use of neat PVA, while the samples having PPSu as a plasticizer were completely amorphous. Further evaluation with ATR-FTIR spectroscopy revealed the formation of significant intermolecular interactions between the API and the PVA-PPSu matrix, which could explain the system’s physical stability during storage. Finally, dissolution studies, conducted under nonsink conditions, revealed that the use of PVA-PPSu is able to maintain DRN’s sustained supersaturation for up to 8 h.

Anticrystal Engineering of Ketoprofen and Ester Local Anesthetics: Ionic Liquids or Deep Eutectic Mixtures?

Ionic liquids (ILs) and deep eutectic mixtures (DEMs) are potential solutions to the problems of low solubility, polymorphism, and low bioavailability of drugs. The aim of this work was to develop and investigate ketoprofen (KET)-based ILs/DEMs containing an ester local anesthetic (LA): benzocaine (BEN), procaine (PRO) and tetracaine (TET) as the second component. ILs/DEMs were prepared via a mechanosynthetic process that involved the mixing of KET with an LA in a range of molar ratios and applying a thermal treatment. After heating above the melting point and quench cooling, the formation of supercooled liquids with Tgs that were dependent on the composition was observed for all KET-LA mixtures with exception of that containing 95 mol% of BEN. The KET-LA mixtures containing either ≥ 60 mol% BEN or 95 mol% of TET showed crystallization to BEN and TET, respectively, during either cooling or second heating. KET decreased the crystallization tendency of BEN and TET and increased their glass-forming ability. The KET-PRO systems showed good glass-forming ability and did not crystallize either during the cooling or during the second heating cycle irrespective of the composition. Infrared spectroscopy and molecular modeling indicated that KET and LAs formed DEMs, but in the KET-PRO systems small quantities of carboxylate anions were present.

Prediction and Experimental of Yield Strengths of As-Quenched 7050 Aluminum Alloy Thick Plates after Continuous Quench Cooling

The aim of this study was to predict the yield strength of as-quenched aluminum alloys according to their continuous quench cooling path. Our model was established within the framework of quench factor analysis (QFA) by representing a quenching curve as a series of consecutive isothermal transformation events and adding the yield strength increments after each isothermal step to predict the yield strength after continuous quench cooling. For simplification; it was considered that the effective hardeners during quenching were the nanosized solute clusters formed at low temperatures, whereas the other coarse precipitates were neglected. In addition, quenching tests were conducted on aluminum plates with different thicknesses. The predictions were compared with the experimental measurements, and the results showed that the predictions fit the measurements well for the 40- and 80-mm-thick plates but overestimated the as-quenched yield strength at the mid-thickness of the 115-mm-thick plates.

Numerical Simulation of Heat Treatment Process of Aluminium Profiles

The paper deals with the simulation of cooling processes of the aluminium profiles inside the water quench. Cooling of profile surfaces is performed by water spray, which is created by mixing a water and an air in a nozzles. Formulas were found in literature, modified and applied to a given problem that significantly simplified a solution. The task of numerical simulations was to determine temperature and velocity profile on aluminium profile surfaces for establishing of the heat transfer coefficient which was used as the convective boundary condition necessary to solve the heat transfer in the aluminium profile by finite element method. The difference between FEM and CFD results is up to 10%.

Improvement of Adhesive Wear Behavior by Variable Heat Treatment of a Tool Steel for Sheet Metal Forming

Vanadis 10 steel is a powder metallurgy (PM) processed tool steel. It is a ledeburitic steel with 8% Cr and 10% V. By deliberately varying the process parameters related to the quenching, tempering, and nitriding of these steels, the aim of this study is to determine which of these parameters have a significant influence on its adhesive wear resistance. The research methodology employed was a Design of Experiments (DoE) with six factors and two levels for each factor. The tempering temperature, number of temperings, and carrying out of a thermochemical nitriding treatment were found to have a significant effect. To increase adhesive wear resistance, austenitization at 1100 °C with air cooling is recommended, followed by three temperings at 500 °C and a subsequent nitriding treatment. It should be noted that the quench cooling medium does not have a significant influence on wear resistance. Furthermore, (Fe,Cr)7C3 (M7C3 carbides) are transformed into carbonitrides during nitriding. However, (Fe,V)C (MC carbides) are not affected by this nitriding process.

Optimization, by Means of a Design of Experiments, of Heat Processes to Increase the Erosive Wear Resistance of White Hypoeutectic Cast Irons Alloyed with Cr and Mo.

To identify the design parameters in heat treatments that have a significant effect on the erosive wear resistance of hypoeutectic high chromium white cast irons, a design of experiment was applied to a white cast iron with 18wt.% Cr and 2wt.% Mo. The analyzed factors were the destabilization heat treatment of austenite (1000 or 1100 °C, for 4 or 8 h), different quench cooling media (in air or oil), different tempering treatments (200 or 500 °C, for 3 or 6 h), and the application of an ionic nitriding treatment. Despite what was expected, the nitriding treatment was not found to have a significant effect on said wear resistance. However, it is concluded that the highest wear resistance is obtained with the shortest dwell time at the destabilization temperature (4 h), quenching in oil, and with the shortest tempering times (3 h). Among the nitrided samples, the highest nitrided layer thicknesses were obtained when the destabilization temperature of the austenite was 1000 °C and the tempering temperature was 200 °C.