The Impact of the Lubrication Step With Magnesium Stearate on the Quality Target Product Profile of a Modified Release Oral Dosage Form Containing a BCS Class Ii Active Pharmaceutical Ingredient

Abstract

Magnesium stearate is an excipient widely used in the pharmaceutical industry, due to its lubrication proprieties. The aim of the study is to evaluate the impact of the lubrication step with magnesium stearate on the Quality Target Product Profile of a modified release oral dosage form containing a BCS Class II active pharmaceutical ingredient and to determine the critical process parameters correlated to the lubrication step. In this context, experimental batches at industrial scale and pilot scale batches were manufactured with two different sorts of magnesium stearate in concentration of approximately 0.5% ( w/w). Based on the experimental results, the over-lubrication phenomena was observed only during the manufacturing of batches with magnesium stearate with lower particle size distribution (~ 1 µm) and higher surface area. The over-lubrication had an higher impact on the physical parameters of the core tablets, such as resistance to crushing. Furthermore, the direct proportionality between the compressing settings and the resistance to crushing parameter was observed to be altered by the lubrication process. Due to the fact the over lubrication phenomena is dependent to the functional-related characteristics of magnesium stearate it can be concluded that the two magnesium stearate sorts cannot be interchangeable, for a tablet matrix with a majority plastic character during compression step. RezumatStearatul de magneziu este un excipient utilizat pe scară largă în industria farmaceutică, datorită proprietăților de lubrifiere. Scopul studiului este de a determina influența procesului de lubrifiere cu stearat de magneziu asupra profilului de calitate al unui produs finit cu cedare modificată și administrare per os, care conține o substanță activă din clasa biofarmaceutică II si de a defini parametrii de proces corelați cu procesul de lubrifiere considerați critici. În această direcție, au fost procesate serii experimentale la scală industrială și serii pilot cu o concentrație de stearat de magneziu de aproximativ 0,5% (m/m). În urma rezultatelor obținute, fenomenul de supra-lubrifiere a fost observat doar pentru seriile procesate cu stearat de magneziu cu dimensiuni de particule mai mici (~ 1 µm) și cu o suprafață specifică mai mare. Procesul de supra-lubrifiere a influențat semnificativ parametrii fizici ale comprimatelor nucleu, precum rezistența mecanică. Proporționalitatea directă dintre setările echipamentului de comprimare și rezistența mecanică a fost redusă de procesul de lubrifiere. Din cauza faptului că procesul de lubrifiere este dependent de caracteristicile legate de funcționalitate ale stearatului de magneziu, se poate concluziona că cele două tipuri de stearat de magneziu nu sunt interschimbabile, în cazul unei matrice cu componenți care prezintă caracter majoritar plastic în timpul etapei de comprimare.

Evaluation of the Impact of the Inlet Air Humidity During Coating Step on the in Vitro Dissolution of Modified-Release Film-Coated Pellets Containing a BCS Class I Active Substance

“…In particular cases, the gastro-resistance is needed to ensure a targeted delivery of the drug [1,9], to provide a delayed release component in the formulation [20,21] or to prevent the interaction of the active substance with pepsin and peptones [17]. These excipients can be either ionizable polymers such as polymethacrylates [11,18], cellulose derivatives like cellulose acetate phthalate, cellulose acetate trimellitate or other esters containing hydroxypropyl methylcellulose phthalate or hydroxypropyl methylcellulose acetate succinate [7], polyvinyl derivatives such as polyvinyl acetate phthalate [14] or excipients that are insoluble in acidic media, but soluble at various alkaline pH such as acetyltriethyl citrate, ceresin (mineral wax), glyceryl behenate, shellac (a polyester resin), tributyl citrate and zein (aminoacidic structure) [5,6,10]. The evaluated formulation for this study is a low dose modified release oral dosage form containing as model drug a BCS I active pharmaceutical ingredient, namely tamsulosin hydrochloride, formulated as film-coated pellets.…”