Three-dimensional printing of ramipril tablets by fused deposition modeling

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Introduction. Ebastine is a second-generation antihistamine drug available in the form of orally disintegrating tablets and film-coated tablets. Ebastine substance exhibits high bioavailability, but low solubility in water and gastrointestinal tract media. The technology of solid dispersions based on polymer carriers by hot melt extrusion is proposed to solve the problem of ebastine low solubility.Aim. Composition development of extrudate and its production technology to create an amorphous solid dispersion of ebastine in oder to increase the recovery rate and bioavailability.Materials and methods. Ebastin micronized (JSC "Active Component", Russia); ebastin crystalline (Arevipharma GmbH, Germany); VIVAPHARM® PVP/VA 64 (JRS Pharma GMbH & Co. KG, Germany). Extrudates were obtained on a HAAKE™ miniCTW co-rotating twin-screw laboratory extruder (Thermo Fisher Scientific, Germany). Extrudates were studied by differential scanning calorimetry, synchronous thermal analysis, powder X-ray diffraction and FTIR-spectroscopy. The quantitative content of the active ingredient was determined by spectrophotometry. The content of related impurities in the amorphous solid dispersion of ebastine was determined by HPLC.Results and discussion. The technology of amorphous solid dispersion of ebastine by hot melt extrusion was developed. The pharmacokinetic properties of ebastine were significantly improved. The process of obtaining solid dispersion with 20 % of ebastine was optimized in order to reduce the content of impurities in the extrudate.Conclusion. The maximum concentration of ebastine for proper quality amorphous solid dispersion based on PVP/VA64 amounted to 20 %. Obtaining a solid dispersion by hot melt extrusion with ebastine content in PVP/VA64 higher than 30 % is impossible because the melt does not possess the glass transition property.

Section: фармацевтическая технология Pharmaceutical Technologyunclassified

Composition and Technology Development for Obtaining Amorphous Solid Dispersion of Ebastine by Hot Melt Extrusion to Increase Dissolution Rate

Gusev,

Aliev,

Generalova

et al. 2023

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“…В области фармацевтической промышленности трехмерная печать дает возможность внести значительный технологический вклад в разработку и производство лекарств [6,7]. Данная технология позволяет разрабатывать новые ЛФ, системы доставки лекарств, создавать ткани и органы [8,9]. Дополнительными преимуществами являются экономическая эффективность, высокая производительность, большой выбор объектов проектирования и производства [10].…”

Section: фармацевтическая технология Pharmaceutical Technologyunclassified

Development of Suppositories Silicone Molds Using Additive Technologies

Gusev

Terenteva

Maimistov

et al. 2022

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Introduction. In modern practice, suppositories are prepared by hand rolling method or fusion. 3D printing can overcome the disadvantages of traditional suppository manufacturing methods and solve the problems of personalization. 3D printing makes it possible to manufacture drug-loaded suppositories without the use of molds or other physical support. The current studies have a number of limitations, and the printing of one suppository requires a long time. This report proposes a method of 3D modeling and 3D printing to produce personalized suppositories by fusion.Aim. Various sizes and shapes suppositories silicone molds development by molding method from hydrophilic, lipophilic and amphiphilic bases.Materials and methods. Suppository bases: cocoa butter (Luker, Colombia), polyethylene glycol (PEG) 1500 (Merck KGaA, Germany), PEG-400 (Merck KGaA, Germany), Witepsol H-15 (Chimmed Group, Russia); pharmaceutical substance: paracetamol (Hebei Jiheng (Group) Pharmaceutical Co. Ltd, China); filaments for 3D printing: polyethylene terephthalate (PET-G natural, LLC "PrintProdakt", Russia); silicone two-component platinum, hardness Shore 30A (China); solvents: Acetonitrile Grade HPLC (Merck KGaA, Germany). The design of the both casting and master molds of suppositories was carried out using the KOMPAS-3D version 17.1. Master molds were printed by Picaso PRO 250 and Picaso X Pro 3D printers. Mold segments were obtained by filling master molds with a mixture of two-component silicone. Suppositories were obtained by molding method. Their average weight and standard deviation were determined. Paracetamol concentration in suppositories was carried out by UV spectrophotometry on a UV-1240 mini spectrophotometer (Shimadzu, Япония). Silicone molds were soaked and washed in hot water with surfactants. Washouts from the molds were taken by soaking the mold.Results and discussion. The torpedo-shaped form was chosen as the model form of suppositories. For the chosen form, three volumes of suppositories were designed: 3.32 ml; 1.5 ml and 0.25 ml. Silicone molds were designed and manufactured for all volumes. The cast suppositories were examined for compliance with the regulatory documentation for the dosage form, the average weight and mass uniformity were evaluated. Suppositories with paracetamol were made. A procedure for cleaning the obtained silicone molds has been developed.Conclusion. The resulting silicone molds make it possible to obtain suppositories in accordance with the regulatory documentation for the suppositories. Silicone molds have significant advantages compared to analogues of metal or polymeric molds.

Development and Validation of HPLC Method for Identification of Ramipril in Printed Tablets and Filaments

Tihonova

Terenteva

Gusev

et al. 2022

Introduction. 3D printing has shown its usefulness as a drug manufacturing technology over the past decade. However, the lack of regulated methods for quality control of finished printed drugs imposes a limitation on the widespread use of 3D printing methods in pharmaceutical practice. Thus, the development of methods for the analysis of printed dosage forms is of interest in pharmaceutical development.Aim. To develop a specific method for the determination of ramipril in filaments and printlets by HPLC.Materials and methods. Substance: ramipril. Excipients: Kollidon® VA 64, Kollidon® CL-F, PEG-1500, sodium carbonate anhydrous, Poloxamer-188, sodium stearyl fumarate. Reagents: hydrochloric acid, acetonitrile for ultra-HPLC, sodium octanesulfonate for HPLC, orthophosphoric acid 85 %, sodium perchlorate analytical grade, triethylamine. Standard: ramipril USP (No 1598303).Results and discussion. A special HPLC method in accordance with an ion-pair reagent (sodium octanesulfonate) for the determination of ramipril in the composition of filaments and printets was proposed.Conclusion. The developed chromatographic method should be adapted for ramipril release determination. This method can be used to quantify ramipril in further studies.