TY - JOUR AU - Hassan, Alharith A. A. AU - Sovány, Tamás AU - Pamlényi, Krisztián AU - Deák, Martin AU - Varga, Viktória AU - Csapó, Edit AU - Regdon, Géza (ifj.) AU - Pannonhalminé Csóka, Ildikó AU - Kristó, Katalin TI - QbD Approach-Based Preparation and Optimization of Hydrophobic Ion-Pairing Complex of Lysozyme with Sodium Dodecyl Sulphate to Enhance Stability in Lipid-Based Carriers JF - PHARMACEUTICS J2 - PHARMACEUTICS VL - 16 PY - 2024 IS - 5 SP - 589 SN - 1999-4923 DO - 10.3390/pharmaceutics16050589 UR - https://m2.mtmt.hu/api/publication/34832111 ID - 34832111 AB - Hydrophobic ion pairing (HIP) complexation was found to be an efficient approach in modulating the release and enhancing the stability and encapsulation of hydrophilic macromolecules such as proteins in hydrophobic nano/microcarriers. The present work strives to develop and optimize the preparation of the HIP complex of the antimicrobial enzyme lysozyme (LYZ) with the ion-pairing agent (IPA) sodium dodecyl sulphate (SDS) relying on the quality-by-design (QbD) approach. The quality target product profile (QTPP) includes the achievement of maximal lipophilicity in a reversible manner to enable the maintenance of biological activity. The related critical quality attributes (CQAs) were defined as complexation efficacy, complex stability, enzyme recovery and activity. Three risk assessment (RA) tools were used to identify and rank the critical process parameters (CPPs) and critical material attributes (CMAs). From this assessment, the pH of the medium, LYZ:SDS molar ratio and drying conditions were determined as high-risk factors that need to be investigated. To the best of our knowledge, for the first time, electrostatic titration was used as a smart approach to determine the optimum molar ratio at different pH values. Based on the predefined CQAs, pH 8 with an LYZ/SDS molar ratio of 1:8 was found to be the optimal condition for complexation efficiency and recovery (%) of a biologically active enzyme. A cost-effective drying process based on a ventilated oven was developed, which resulted in complex qualities comparable to those obtained by the commonly used freeze-drying method. In a nutshell, the optimum conditions for the preparation of the LYZ/SDS HIP complex were efficiently facilitated by the rational application of QbD principles and the utilization of efficient electrostatic titration and ventilated oven-drying methods. LA - English DB - MTMT ER - TY - CHAP AU - Mahmoud, Azza AU - Pannonhalminé Csóka, Ildikó AU - Regdon, Géza (ifj.) AU - Kristó, Katalin ED - Varga, Patrícia Orsolya ED - Szalai, Boglárka ED - Uhljar, Luca Éva TI - High shear granulation as a promising technique in the direct pelletization process T2 - VI. Symposium of Young Researchers on Pharmaceutical Technology, Biotechnology and Regulatory Science PB - Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Faculty of Pharmacy CY - Szeged PY - 2024 SP - 40 EP - 40 PG - 65 UR - https://m2.mtmt.hu/api/publication/34657079 ID - 34657079 LA - English DB - MTMT ER - TY - CHAP AU - Hassan, Alharith Abdulraheem Abdulmajeed AU - Kristó, Katalin AU - Deák, Martin AU - Regdon, Géza (ifj.) AU - Varga, Viktória AU - Csapó, Edit AU - Sovány, Tamás ED - Varga, Patrícia Orsolya ED - Szalai, Boglárka ED - Uhljar, Luca Éva TI - Application of QbD Principles in Hydrophobic-Ion Pairing Complexation of Proteins T2 - VI. Symposium of Young Researchers on Pharmaceutical Technology, Biotechnology and Regulatory Science PB - Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Faculty of Pharmacy CY - Szeged PY - 2024 SP - 37 EP - 37 PG - 65 UR - https://m2.mtmt.hu/api/publication/34641372 ID - 34641372 LA - English DB - MTMT ER - TY - JOUR AU - Hassan, Alharith Abdulraheem Abdulmajeed AU - Kristó, Katalin AU - Regdon, Géza (ifj.) AU - Varga, Viktória AU - Csapó, Edit AU - Sovány, Tamás TI - Step by Step Preparation and Optimization of Lysozyme Hydrophobic Ion Pairing Complex JF - MACEDONIAN PHARMACEUTICAL BULLETIN J2 - MACED PHARMA BULL VL - 69 PY - 2023 IS - Suppl. 1 SP - 287 EP - 288 PG - 2 SN - 1409-8695 DO - 10.33320/maced.pharm.bull.2023.69.03.139 UR - https://m2.mtmt.hu/api/publication/34590475 ID - 34590475 LA - English DB - MTMT ER - TY - CONF AU - Mahmoud, Azza AU - Regdon, Géza (ifj.) AU - Kristó, Katalin ED - Benkő, Ernő ED - Regdon, Géza (ifj.) ED - Vasvári, Gábor TI - Application of Pro-CepT granulator for direct pelletization process T2 - VI. Fiatal Technológusok Fóruma: absztraktfüzet PY - 2023 SP - 7 EP - 7 PG - 1 DO - 10.14232/ftf.2023.op1 UR - https://m2.mtmt.hu/api/publication/34191750 ID - 34191750 LA - English DB - MTMT ER - TY - JOUR AU - Hassan, Alharith Abdulraheem Abdulmajeed AU - Kristó, Katalin AU - Ibrahim, Yousif AU - Regdon, Géza (ifj.) AU - Sovány, Tamás TI - Quality by Design-Guided Systematic Development and Optimization of Mucoadhesive Buccal Films JF - PHARMACEUTICS J2 - PHARMACEUTICS VL - 15 PY - 2023 IS - 10 PG - 24 SN - 1999-4923 DO - 10.3390/pharmaceutics15102375 UR - https://m2.mtmt.hu/api/publication/34155909 ID - 34155909 N1 - Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Eötvös u. 6, Szeged, H-6720, Hungary Department of Pharmaceutics, Faculty of Pharmacy, University of Khartoum, P.O. Box 321, Khartoum, Sudan Pharmaceutics Department, Omdurman Islamic University, P.O. Box 382, Omdurman, Sudan Export Date: 13 December 2023 Correspondence Address: Sovány, T.; Institute of Pharmaceutical Technology and Regulatory Affairs, Eötvös u. 6, Hungary; email: sovany.tamas@szte.hu Chemicals/CAS: chitosan, 9012-76-4; citric acid, 126-44-3, 5949-29-1, 77-92-9, 8002-14-0; glycerol, 56-81-5; lidocaine, 137-58-6, 24847-67-4, 56934-02-2, 73-78-9 Tradenames: Avatar 330, Thermo, United States; DLS, VELP Scientifica, Italy; DT700 LH, ERWEKA, Germany; Helios Alpha, Unicam, Hungary; MAC 50 RADWAG, RADWAG Wagi Elektroniczne, Poland Manufacturers: ERWEKA, Germany; Memmert, Germany; Unicam, Hungary; VELP Scientifica, Italy; RADWAG Wagi Elektroniczne, Poland; Thermo, United States; TIBCO, United States Funding details: Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, NKFIA Funding text 1: This research was funded by Project no. TKP2021-EGA-32, implemented with the support provided by the Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund, and financed under the TKP2021-EGA funding scheme. AB - Mucoadhesive buccal films have found increased popularity in pharmaceutical drug delivery due to the several advantages that they possess. The present study strives to develop and optimize chitosan-based mucoadhesive buccal films by relying on quality-by-design (QbD) principles. Previous knowledge and experience were employed to firstly identify the critical quality attributes (CQAs), followed by a thorough risk assessment, which led to the selection of seven critical material attributes and process parameters, namely, the polymer grade and concentration, the plasticizer type and concentration, the citric acid (CA) concentration, the amount of the casted solution, and the drying condition. Their effects on the breaking hardness and mucoadhesivity, selected as CQAs, were investigated in three steps by three designs of the experiment (DoE). The medium molecular weight of chitosan (CH) was the preferred choice in the optimized formulation, and its concentration was the most important factor affecting the CQAs, thickness, and moisture content of the films. It was found that 0.364 g/cm2 was the suitable amount of the casting solution, and its optimum drying conditions were presented in the form of a design space. Glycerol (Gly) was the best choice as a plasticizer, and a design space representing several combinations of CH and CA concentrations that produce films with the required quality was constructed at a fixed concentration of 35% Gly. A formula from this design space was selected and employed to load with two model drugs to test its drug-carrying properties for drugs with different physicochemical characteristics. Uniform drug distribution with an immediate release profile was achieved in both drugs, although one of the CQAs was outside of the specifications in the case of lidocaine-containing film. To summarize, the obtention of the optimum mucoadhesive buccal film based on CH was efficiently facilitated by the rational application of QbD principles and the DoE approach. LA - English DB - MTMT ER - TY - CHAP AU - Ibrahim, Yousif AU - Regdon, Géza (ifj.) AU - Sovány, Tamás AU - Kristó, Katalin AU - Katona, Gábor ED - Varga, Patrícia Orsolya ED - Szalai, Boglárka ED - Uhljar, Luca Éva TI - Gum arabic as novel lysozyme carrier polymer T2 - V. Symposium of Young Researchers on Pharmaceutical Technology, Biotechnology and Regulatory Science PB - Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Faculty of Pharmacy CY - Szeged PY - 2023 SP - 36 EP - 36 PG - 1 DO - 10.14232/syrptbrs.2023.36 UR - https://m2.mtmt.hu/api/publication/34046079 ID - 34046079 LA - English DB - MTMT ER - TY - CHAP AU - Pamlényi, Krisztián AU - Regdon, Géza (ifj.) AU - Jójártné Laczkovich, Orsolya AU - Nemes, Dániel AU - Bácskay, Ildikó AU - Kristó, Katalin ED - Varga, Patrícia Orsolya ED - Szalai, Boglárka ED - Uhljar, Luca Éva TI - Formulation of buccal films in Parkinson’s disease T2 - V. Symposium of Young Researchers on Pharmaceutical Technology, Biotechnology and Regulatory Science PB - Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Faculty of Pharmacy CY - Szeged PY - 2023 SP - 34 EP - 34 PG - 1 DO - 10.14232/syrptbrs.2023.34 UR - https://m2.mtmt.hu/api/publication/34046049 ID - 34046049 LA - English DB - MTMT ER - TY - JOUR AU - Pamlényi, Krisztián AU - Regdon, Géza (ifj.) AU - Jójártné Laczkovich, Orsolya AU - Nemes, Dániel AU - Bácskay, Ildikó AU - Kristó, Katalin TI - Formulation and characterization of pramipexole containing buccal films for using in Parkinson's disease JF - EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES J2 - EUR J PHARM SCI VL - 187 PY - 2023 PG - 12 SN - 0928-0987 DO - 10.1016/j.ejps.2023.106491 UR - https://m2.mtmt.hu/api/publication/34008857 ID - 34008857 N1 - Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Eötvös u. 6., H-6720, Szeged, Hungary Department of Pharmaceutical Technology, University of Debrecen, Nagyerdei krt. 98., H-4032, Debrecen, Hungary Export Date: 1 August 2023 CODEN: EPSCE Correspondence Address: Regdon, G.; Institute of Pharmaceutical Technology and Regulatory Affairs, Eötvös u. 6., H-6720, Hungary; email: geza.regdon@pharm.u-szeged.hu Chemicals/CAS: pramipexole, 104632-26-0, 104632-25-9, 191217-81-9; Drug Carriers; Pramipexole Funding details: 5991 Funding details: Richter Gedeon Talentum Alapítvány, 100822 Funding details: Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, NKFIA, ÚNKP-21-3 Funding details: Innovációs és Technológiai Minisztérium Funding text 1: The publication was funded by The University of Szeged Open Access Fund (FundRef, Grant No. 5991). This research work was supported by Richter Gedeon Talentum Foundation to help me participate in the PhD program (Grant No. 100822 ). This work was also supported by the New National Excellence Program of the Ministry for Innovation and Technology from the Source of the National Research, Development and Innovation Fund (Grant No. ÚNKP-21-3 ). LA - English DB - MTMT ER - TY - JOUR AU - Šahinović, Merima AU - Hassan, Alharith Abdulraheem Abdulmajeed AU - Kristó, Katalin AU - Regdon, Géza (ifj.) AU - Vranić, Edina AU - Sovány, Tamás TI - Quality by Design-Based Development of Solid Self-Emulsifying Drug Delivery System (SEDDS) as a Potential Carrier for Oral Delivery of Lysozyme JF - PHARMACEUTICS J2 - PHARMACEUTICS VL - 15 PY - 2023 IS - 3 PG - 28 SN - 1999-4923 DO - 10.3390/pharmaceutics15030995 UR - https://m2.mtmt.hu/api/publication/33777250 ID - 33777250 N1 - Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Sarajevo, Zmaja od Bosne 8, Sarajevo, 71000, Bosnia and Herzegovina Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Eötvös u 6., Szeged, 6720, Hungary Export Date: 17 June 2023 Correspondence Address: Sovány, T.; Institute of Pharmaceutical Technology and Regulatory Affairs, Eötvös u 6., Hungary; email: sovany.tamas@szte.hu AB - For many years, researchers have been making efforts to find a manufacturing technique, as well as a drug delivery system, that will allow for oral delivery of biopharmaceuticals to their target site of action without impairing their biological activity. Due to the positive in vivo outcomes of this formulation strategy, self-emulsifying drug delivery systems (SEDDSs) have been intensively studied in the last few years as a way of overcoming the different challenges associated with the oral delivery of macromolecules. The purpose of the present study was to examine the possibility of developing solid SEDDSs as potential carriers for the oral delivery of lysozyme (LYS) using the Quality by Design (QbD) concept. LYS was successfully ion paired with anionic surfactant, sodium dodecyl sulphate (SDS), and this complex was incorporated into a previously developed and optimized liquid SEDDS formulation comprising medium-chain triglycerides, polysorbate 80, and PEG 400. The final formulation of a liquid SEDDS carrying the LYS:SDS complex showed satisfactory in vitro characteristics as well as self-emulsifying properties (droplet size: 13.02 nm, PDI: 0.245, and zeta potential: −4.85 mV). The obtained nanoemulsions were robust to dilution in the different media and highly stable after 7 days, with a minor increase in droplet size (13.84 nm) and constant negative zeta potential (−0.49 mV). An optimized liquid SEDDS loaded with the LYS:SDS complex was further solidified into powders by adsorption onto a chosen solid carrier, followed by direct compression into self-emulsifying tablets. Solid SEDDS formulations also exhibited acceptable in vitro characteristics, while LYS preserved its therapeutic activity in all phases of the development process. On the basis of the results gathered, loading the hydrophobic ion pairs of therapeutic proteins and peptides to solid SEDDS may serve as a potential method for delivering biopharmaceuticals orally. LA - English DB - MTMT ER -