This Experimental Magistral Thesis work, done at the company Meda Pharma S.p.A. in the production site of Confienza (PV), concerns the validation of a new procedure to conduct a stability study of a food supplement, in order to verify and ensure compliance in time of safety, efficacy and quality requirements. Are then evaluated the physical, chemical and microbiological parameters expected, based on the application of analytical protocols provided by the ICH Guide Lines (International Conference on Harmonisation), that define what are the stability studies to perform and how to be carried out, so as to using validated and standardized procedures. In accordance with Directive CE n°46 of 10 June 2002 (as amended up to the Regulation CE n°1170 of 30 November 2009), Legislative Decree n°169 of 21 May 2004 at Article 2 defines food supplements as "food products for inclusion in the common diet and which are concentrated sources of nutrients, such as vitamins and minerals, or other substances with a nutritional or physiological effect, in particular, but not exclusively, amino acids, essential fatty acids, fiber and herbal extracts, alone or in combination, in unit dose form". The assumption must be made, if necessary, for example to compensate for a deficient supply of the main nutrients, in sports practice, or to supplement the diet in particular stages of life. Specifically, I focused on the stability study of Estromineral Serena, a food supplement marketed in the form of tablets packaged in PVC/PVDC aluminum blister. The product has been designed with the aim of mitigating the symptoms appearing in menopause through the action of its functional ingredients: Magnolia officinalis Rehder, cortex (dry extract 1.5% in honokiol), Soybean Glycine max L. Merr, semen (dry extract standardized to 40% isoflavones), Lactobacillus sporogenes (Bacillus coagulans LMG S-24828), Magnesium Oxide, Calcium Carbonate and Vitamin D3 present in defined amounts. The frequency of testing is fixed at predetermined intervals: at time 0, then every 3 months for the first year and every 6 months from the second year and subsequent years should be sufficient to cover the validity period indicated on the label; that studies must be conducted in at least three different batches of the same food supplement formulated and packaged in the original packaging proposed for marketing and stored at three different possible temperature and humidity conditions set by the ICH Guide Line Q1A (R2), which simulate those for products to be allocated to the market. The tests to be performed are: titration of Magnolia officinalis, Soy Isoflavones and Vitamin D3 which involves the use of HPLC; the quantitative determination of Calcium and Magnesium ions that adopts a potentiometric method; the assessment of the number of viable spores of Lactobacillus sporogenes that is performed by seeding of GYE agar. In addition, the moisture content is evaluated (through Dryer) and the tablet disintegration/dissolution (through Disintegration Tester). The results obtained were compared with the specifications. Data showed the maintenance of the values within the range established by Circular n°7 of 30 October 2002, for all the different conditions considered and for all evaluated time (six month, the duration of the study). The validation of the procedure came to an end successfully, proving adequate for the conduct of the stability study and able to ensure compliance with the standards of quality, safety and efficacy expected of the finished product.
Il presente lavoro di Tesi Sperimentale Magistrale, svolto presso l'azienda Meda Pharma S.p.A. nel sito produttivo di Confienza (PV), riguarda la convalida di una nuova procedura volta a condurre uno studio di stabilità su un integratore alimentare, in modo da verificarne e garantirne il rispetto nel tempo dei requisiti di sicurezza, efficacia e qualità vantati. Verranno quindi valutati i parametri fisici, chimici e microbiologici attesi, sulla base dell'applicazione di protocolli d'analisi forniti dalle Linee Guida ICH (International Conference on Harmonisation), che definiscono quali sono gli studi di stabilità da eseguire e come effettuarli, così da utilizzare procedure convalidate e standardizzate. Conformemente alla Direttiva CE n°46 del 10 giugno 2002 (e successive modifiche fino al Regolamento CE n°1170 del 30 novembre 2009), il Decreto Legislativo n°169 del 21 maggio 2004 all'articolo 2 definisce gli integratori alimentari quei "prodotti alimentari destinati ad integrare la comune dieta e che costituiscono una fonte concentrata di sostanze nutritive, quali le vitamine e i minerali, o di altre sostanze aventi un effetto nutritivo o fisiologico, in particolare, ma non in via esclusiva, aminoacidi, acidi grassi essenziali, fibre ed estratti di origine vegetale, sia monocomposti che pluricomposti, in forme predosate". L'assunzione deve avvenire all'occorrenza, ad esempio per compensare una alimentazione carente dei nutrienti principali, nella pratica sportiva, o per integrare la dieta in particolari stadi della vita. Nello specifico mi sono concentrata sullo studio di stabilità di Estromineral Serena, un integratore alimentare commercializzato sottoforma di compresse confezionate in blister di alluminio PVC/PVDC. Il prodotto è stato realizzato con la finalità di mitigare l'entità della sintomatologia che compare in menopausa, supplementando la dieta a scopo salutistico attraverso l'azione dei suoi ingredienti funzionali: Magnolia officinalis Rehder, cortex (estratto secco titolato all'1,5% in Honokiolo), Soia Glycine max L. Merr, semen (estratto secco titolato al 40% in Isoflavoni), Lattobacillus sporogenes (Bacillus coagulans LMG S-24828), Ossido di Magnesio, Carbonato di Calcio e Vitamina D3 presenti in quantità definite. La frequenza dei test è fissata a intervalli di tempo prestabiliti: al tempo 0, poi ogni 3 mesi per il primo anno e ogni 6 mesi dal secondo anno e per gli anni successivi che devono essere sufficienti a coprire il periodo di validità indicato in etichetta; bisogna che gli studi vengano condotti su almeno tre lotti differenti dello stesso integratore alimentare formulati e confezionati nel packaging originale proposto per la commercializzazione e conservati a 3 diverse possibili condizioni termoigrometriche fissate dalla Linea Guida ICH Q1A (R2), che simulino quelle previste per i prodotti da destinarsi al mercato. Le analisi da eseguire sono: la titolazione di Magnolia officinalis, Isoflavoni di Soia e Vitamina D3 che implica l'uso dell'HPLC; la determinazione quantitativa degli ioni Calcio e Magnesio che adotta un metodo potenziometrico; la valutazione del numero delle spore vitali di Lattobacillus sporogenes che viene eseguita tramite semina su GYE agar. In aggiunta, viene valutato il contenuto di umidità (tramite Essiccatore) e la disgregazione/dissoluzione delle compresse (tramite Disintegration Tester). I risultati ottenuti sono stati confrontati con le specifiche. I dati hanno evidenziato il mantenimento dei valori entro range stabiliti dalla Circolare n°7 del 30 ottobre 2002, per tutte le differenti condizioni considerate e per tutto il tempo valutato (6 mesi, la durata del mio tirocinio). La convalida della procedura applicata si è quindi conclusa con esito positivo, rivelandosi adeguata per la conduzione dello studio di stabilità e in grado di garantire il rispetto dei parametri di qualità, sicurezza ed efficacia attesi del prodotto finito.
CONVALIDA DI UNA PROCEDURA PER STUDI DI STABILITÀ DELL'INTEGRATORE ALIMENTARE ESTROMINERAL SERENA
MONTALDI, VANESSA
2015/2016
Abstract
This Experimental Magistral Thesis work, done at the company Meda Pharma S.p.A. in the production site of Confienza (PV), concerns the validation of a new procedure to conduct a stability study of a food supplement, in order to verify and ensure compliance in time of safety, efficacy and quality requirements. Are then evaluated the physical, chemical and microbiological parameters expected, based on the application of analytical protocols provided by the ICH Guide Lines (International Conference on Harmonisation), that define what are the stability studies to perform and how to be carried out, so as to using validated and standardized procedures. In accordance with Directive CE n°46 of 10 June 2002 (as amended up to the Regulation CE n°1170 of 30 November 2009), Legislative Decree n°169 of 21 May 2004 at Article 2 defines food supplements as "food products for inclusion in the common diet and which are concentrated sources of nutrients, such as vitamins and minerals, or other substances with a nutritional or physiological effect, in particular, but not exclusively, amino acids, essential fatty acids, fiber and herbal extracts, alone or in combination, in unit dose form". The assumption must be made, if necessary, for example to compensate for a deficient supply of the main nutrients, in sports practice, or to supplement the diet in particular stages of life. Specifically, I focused on the stability study of Estromineral Serena, a food supplement marketed in the form of tablets packaged in PVC/PVDC aluminum blister. The product has been designed with the aim of mitigating the symptoms appearing in menopause through the action of its functional ingredients: Magnolia officinalis Rehder, cortex (dry extract 1.5% in honokiol), Soybean Glycine max L. Merr, semen (dry extract standardized to 40% isoflavones), Lactobacillus sporogenes (Bacillus coagulans LMG S-24828), Magnesium Oxide, Calcium Carbonate and Vitamin D3 present in defined amounts. The frequency of testing is fixed at predetermined intervals: at time 0, then every 3 months for the first year and every 6 months from the second year and subsequent years should be sufficient to cover the validity period indicated on the label; that studies must be conducted in at least three different batches of the same food supplement formulated and packaged in the original packaging proposed for marketing and stored at three different possible temperature and humidity conditions set by the ICH Guide Line Q1A (R2), which simulate those for products to be allocated to the market. The tests to be performed are: titration of Magnolia officinalis, Soy Isoflavones and Vitamin D3 which involves the use of HPLC; the quantitative determination of Calcium and Magnesium ions that adopts a potentiometric method; the assessment of the number of viable spores of Lactobacillus sporogenes that is performed by seeding of GYE agar. In addition, the moisture content is evaluated (through Dryer) and the tablet disintegration/dissolution (through Disintegration Tester). The results obtained were compared with the specifications. Data showed the maintenance of the values within the range established by Circular n°7 of 30 October 2002, for all the different conditions considered and for all evaluated time (six month, the duration of the study). The validation of the procedure came to an end successfully, proving adequate for the conduct of the stability study and able to ensure compliance with the standards of quality, safety and efficacy expected of the finished product.È consentito all'utente scaricare e condividere i documenti disponibili a testo pieno in UNITESI UNIPV nel rispetto della licenza Creative Commons del tipo CC BY NC ND.
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https://hdl.handle.net/20.500.14239/22485