Razvoj novega galenskega zdravila z esketaminom v bolnišnični lekarni Univerzitetnega kliničnega centra Ljubljana

Verk, Ema (author), Gašperlin, Mirjana (mentor), Tršan, Mateja (co-mentor)

Jeseni 2020 se je v bolnišnični lekarni UKC Ljubljana pojavila potreba po hitrem razvoju novega galenskega zdravila z esketaminom za kontinuirano infuzijo. Esketamin se je uporabljal za indukcijo anestezije ob intubaciji in vzdrževanje sedacije med mehansko ventilacijo pri najbolj prizadetih bolnikih s COVID-19, posledično se je v tem obdobju njegova uporaba močno povečala. Prednosti uporabe esketamina pri bolnikih s COVID-19 v primerjavi z drugimi anestetiki oz. sedativi npr. opioidi so njegovi ugodni učinki na kardiovaskularni in respiratorni sistem. Esketamin med sedacijo vzdržuje krvni tlak in srčno frekvenco, povzroča bronhodilatcijo in ohranja reflekse dihalnih poti, poleg tega pa ima za bolnike s COVID-19 tudi koristne protivnetne in imunosupresivne učinke. Namen magistrske naloge je bil ocena tveganja, razvoj recepture in proizvodnega procesa za nov galenski izdelek ESKETAMIN 25 mg/mL, 50 mL raztopina za injiciranje/infundiranje, ter razvoj metod za analizo zdravilne učinkovine esketaminijevega klorida, polizdelka in končnega izdelka. Izvedli smo tudi 12-mesečno stabilnostno študijo izdelka pri sobnih pogojih. Uporabljene metode so bile: organoleptični pregled, določanje pH raztopine, določanje koncentracije esketamina, določanje koncentracije kloridnih ionov, določanje specifične optične rotacije raztopine, določanje čistosti zdravilne učinkovine in izdelka s spektrofotometrično analizo, test na sterilnost in test na bakterijske endotoksine. Za vse parametre smo določili meje sprejemljivosti. V analizi polizdelka, končnega izdelka in med stabilnostno študijo so vzorci ustrezali postavljenim pogojem za organoleptični pregled in spektrofotometrično analizo čistosti. PH, koncentracija esketamina in kloridnih ionov ter specifična optična rotacija so bili znotraj specifikacijskih mej. Končni izdelek je tudi po 12 mesecih ostal sterilen in apirogen. V stabilnostni študiji smo potrdili, da je rok uporabe galenskega izdelka ESKETAMIN 25 mg/mL, 50 mL raztopina za injiciranje/infundiranje vsaj 12 mesecev.

• Language: Slovenian
• Keywords: galensko zdravilo, bolnišnična lekarna, esketamin, kontinuirana infuzija, stabilnost
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2022
• PID: 20.500.12556/RUL-141427
• Publication date in RUL: 29.09.2022

Secondary language

• Language: English
• Title: Development of a new galenic drug with esketamine in University Medical Centre Ljubljana hospital pharmacy

Abstract

In autumn of 2020, a need arose at the hospital pharmacy of University Medical Centre Ljubljana to rapidly develop a new galenic drug with esketamine for continuous infusion. Esketamine was used for induction of anaesthesia at intubation and maintenance of sedation during mechanical ventilation in the most affected patients with COVID-19, and consequently its use increased dramatically during this period. The advantages of using esketamine in COVID-19 patients compared to other anaesthetics or sedatives, e.g. opioids, are its beneficial effects on the cardiovascular and respiratory systems. During sedation esketamine maintains blood pressure and heart rate, induces bronchodilatation and preserves airway reflexes and has anti-inflammatory and immunosuppressive effects, which are beneficial for COVID-19 patients. The aim of the masters thesis was risk assessment of the new galenic drug, developing a formulation and manufacturing process for a new galenic product ESKETAMIN 25 mg/mL, 50 mL solution for injection/infusion, and development of methods for the analysis of the active substance esketamine hydrochloride, the intermediate and the final product. A 12-month stability study of the product at ambient conditions was also carried out. The methods used were: organoleptic examination, pH determination of the solution, determination of the concentration of esketamine, determination of the concentration of chloride ions, determination of the specific optical rotation of the solution, determination of the purity of the active substance and the product by spectrophotometric analysis, sterility test and test for bacterial endotoxins. Acceptance limits have been established for all parameters. In the analysis of the intermediate, the final product and during the stability study, the intermediate/product met the conditions for organoleptic examination and spectrophotometric purity analysis, the pH, the concentration of esketamine and chloride ions and the specific optical rotation were within the specification limits. The final product remained sterile and apyrogenic after 12 months. In a stability study, we confirmed that the shelf life of the ESKETAMIN 25 mg/mL, 50 mL solution for injection/infusion final product is at least 12 months.

• Keywords: galenic drug, hospital pharmacy, esketamine, continuous infusion, stability