(Trans)dermal patches (TP) are well-known pharmaceutical preparations designed to provide prolonged drug delivery through the skin to achieve a local, regional or systemic effect. TPs are often preferred to other topically-applied dosage forms since they make it possible to predetermine the drug absorption kinetic and to define the treated area. Thus, TPs can reduce the side effects on healthy skin and due to an undesired systemic drug absorption when localized cutaneous diseases or injuries have to be treated. TPs are produced by a solvent casting technique, but they cannot be easily compounded since, after solvent evaporation, significant modifications of the adhesive matrix, and therefore, of the drug release and adhesive properties, can occur over an unknown period of time, ranging from some days to weeks. These alterations cannot be monitored in a pharmacy setting. This work demonstrated the feasibility of the extemporaneous preparation of (trans)dermal patches by hot-melt ram extrusion 3D printing [1]. This technology makes it possible to easily define both the patch geometry and the dose according to patient needs. The TP preparation consists of three simple technological operations: (i) the drug, the film-forming material (Eudragit (Eu) RL, RS or blends thereof) and the plasticizer (triacetin, TRI, or try-butyl citrate, TBC), which confers the adhesive properties [2], are mixed in a mortar; (ii) the mixture is fed in to the chamber of the ramextruder and heated to 90 °C; (iii) the melt mixture is printed with the desired geometry (thickness: 50 μm) on the backing layer and coupled with the release liner. The adhesive properties of printed patches were investigated by shear and 180°-peel adhesion tests. The results showed that patches with suitable adhesive properties can be printed using 40% w/w of TRI or 50% w/w of TBC. The TRI containing patches showed higher shear adhesion values than TBC ones (p < 0.05). Since high values of shear adhesion are essential for the patch permanence onto the skin, TRI (40% w/w) was selected to print drug-loaded patches, using 2.34% w/w of ketoprofen (KP) and 3% of nicotine (NT) as model compounds. Neither drug affected the patch adhesive properties, even if a reduction of shear adhesion up to 8-folds was observed based on the drug type and the EuRL/EuRS ratio. Finally, the in vitro release studies showed that the EuRL/EuRS ratio impacted significantly on the release rate of both the tested drugs. According to the well-known characteristics of the two copolymers, the higher the concentration of EuRL in the matrix, the higher the release rate of both KP and NT. References: [1] Musazzi, U.M.; Selmin, F.; Ortenzi, M.A.; Mohammed, G.K.; Franzé, S.; Minghetti, P.; Cilurzo, F. Personalized orodispersible films by hot melt ram extrusion 3d printing. Int. J. Pharm. 2018, 551, 52–59. [2] Quaroni, G.M.G.; Gennari, C.G.M.; Cilurzo, F.; Guylaine, D.; Creton, C.; Minghetti, P. Tuning the rheological properties of an ammonium methacrylate copolymer for the design of adhesives suitable for transdermal patches. Eur. J. Pharm. Sci. 2018, 111, 238–246.

Compounding of (Trans)Dermal Patches by Hot-Melt Ram Extrusion 3D Printing / U.M. Musazzi, C.G.M. Gennari, P. Minghetti, F. Cilurzo. - In: PHARMACEUTICS. - ISSN 1999-4923. - 11:(2019 Jan 21), pp. 48.15-48.16. ((Intervento presentato al convegno Advances in Drug Delivery and Biomaterials: Facts and Vision tenutosi a Padova nel 2018.

Compounding of (Trans)Dermal Patches by Hot-Melt Ram Extrusion 3D Printing

U.M. Musazzi
Primo
;
C.G.M. Gennari;P. Minghetti;F. Cilurzo
2019

Abstract

(Trans)dermal patches (TP) are well-known pharmaceutical preparations designed to provide prolonged drug delivery through the skin to achieve a local, regional or systemic effect. TPs are often preferred to other topically-applied dosage forms since they make it possible to predetermine the drug absorption kinetic and to define the treated area. Thus, TPs can reduce the side effects on healthy skin and due to an undesired systemic drug absorption when localized cutaneous diseases or injuries have to be treated. TPs are produced by a solvent casting technique, but they cannot be easily compounded since, after solvent evaporation, significant modifications of the adhesive matrix, and therefore, of the drug release and adhesive properties, can occur over an unknown period of time, ranging from some days to weeks. These alterations cannot be monitored in a pharmacy setting. This work demonstrated the feasibility of the extemporaneous preparation of (trans)dermal patches by hot-melt ram extrusion 3D printing [1]. This technology makes it possible to easily define both the patch geometry and the dose according to patient needs. The TP preparation consists of three simple technological operations: (i) the drug, the film-forming material (Eudragit (Eu) RL, RS or blends thereof) and the plasticizer (triacetin, TRI, or try-butyl citrate, TBC), which confers the adhesive properties [2], are mixed in a mortar; (ii) the mixture is fed in to the chamber of the ramextruder and heated to 90 °C; (iii) the melt mixture is printed with the desired geometry (thickness: 50 μm) on the backing layer and coupled with the release liner. The adhesive properties of printed patches were investigated by shear and 180°-peel adhesion tests. The results showed that patches with suitable adhesive properties can be printed using 40% w/w of TRI or 50% w/w of TBC. The TRI containing patches showed higher shear adhesion values than TBC ones (p < 0.05). Since high values of shear adhesion are essential for the patch permanence onto the skin, TRI (40% w/w) was selected to print drug-loaded patches, using 2.34% w/w of ketoprofen (KP) and 3% of nicotine (NT) as model compounds. Neither drug affected the patch adhesive properties, even if a reduction of shear adhesion up to 8-folds was observed based on the drug type and the EuRL/EuRS ratio. Finally, the in vitro release studies showed that the EuRL/EuRS ratio impacted significantly on the release rate of both the tested drugs. According to the well-known characteristics of the two copolymers, the higher the concentration of EuRL in the matrix, the higher the release rate of both KP and NT. References: [1] Musazzi, U.M.; Selmin, F.; Ortenzi, M.A.; Mohammed, G.K.; Franzé, S.; Minghetti, P.; Cilurzo, F. Personalized orodispersible films by hot melt ram extrusion 3d printing. Int. J. Pharm. 2018, 551, 52–59. [2] Quaroni, G.M.G.; Gennari, C.G.M.; Cilurzo, F.; Guylaine, D.; Creton, C.; Minghetti, P. Tuning the rheological properties of an ammonium methacrylate copolymer for the design of adhesives suitable for transdermal patches. Eur. J. Pharm. Sci. 2018, 111, 238–246.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/614894
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