- Email: [email protected]
Taste masking of isoniazid by hot melt extrusion and spray drying – A comparative study
1142
Abstracts / International Journal of Pharmaceutics 511 (2016) 1127–1150
histone deacetylase (HDAC) inhibitor, was shown to significantly reduce fibrosis and promote compensatory muscle regeneration. Italfarmaco has developed a Givinostat oral liquid formulation being used as investigational medicinal product in the clinical study DSC/11/2357/43 (EudraCT no. 2012-002566-12) “A two parts study to assess the safety and tolerability, pharmacokinetics, and effects on histology and different clinical parameters of Givinostat in ambulant children with Duchenne Muscular Dystrophy”. This poster highlights the main development efforts leading to the obtainment of an acceptable oral liquid formulation for clinical development and the result of the assessment questionnaire on acceptability of the formulation submitted to children and parents during the course of the study. Method: API: Givinostat (as hydrochloride monohydrate) Excipients: compendial excipients Formulation development: based upon age appropriateness of formulation according to “Reflection Paper: Formulation of choice for the paediatric population” (EMEA/CHMP/PEG/194810/2005). Compliance (acceptability) of the formulation was assessed through a questionnaire submitted after 9 and 12 months of treatment during the course of the clinical study. Particularly children were requested to rank the taste of the formulation and parents to provide their feedback on both the taste and on the easiness of the administration procedure. Results and conclusions: Italfarmaco decided to develop an oral liquid formulation of Givinostat as oral liquid formulation is either ranked as “dosage form of choice” (children pre-school) or as “preferred acceptability” (children school and adolescents) in terms of acceptability. Italfarmaco has therefore developed a Givinostat oral liquid formulation allowing for an appropriate volume of administration (≥0.5 mL and ≤10 mL), wide dosage flexibility (that largely covers the anticipated doses for the clinical study) and an acceptable chemical stability at refrigerated conditions. Sweetening and flavouring agents (to cover the bitter taste and to give a basic sensation of sweet, see “Recommendation for selection and use of flavours in paediatric formulation, EMEA/CHMP/PEG/194810/2005) were added to possibly improve palatability characteristics. The results of the assessment questionnaire after 12 months treatment show an overall good acceptability of the developed formulation both in terms of taste and easiness of administration. The formulation can therefore be proposed for further clinical development. http://dx.doi.org/10.1016/j.ijpharm.2016.06.094 Abstract ID: 35 Taste masking of isoniazid by hot melt extrusion and spray drying – A comparative study Alison Keating, Duncan Craig, Catherine Tuleu, Claire Forbes, Barry Aldous, Min Zhao UCL School of Pharmacy, United Kingdom Introduction: Taste masked polymeric formulations have become increasingly popular in improving paediatric patient compliance. Hot melt extrusion (HME) is often recommended for producing such formulations while spray drying (SD) has not been extensively applied in this area. Hence it is of great significance to undertake a comparative study to investigate the different taste masking effects between the two processes. Purpose: To produce and compare polymeric formulations of isoniazid (IZD) by HME and SD for masking the bitter taste of IZD and understand the corresponding mechanisms. Method: Formulations of IZD with Soluplus (SLP) or Eudragit EPO (EPO) were prepared at a range of drug loadings by HME
(ThermoScientific, UK). Formulations at 20% drug loading (the most effective ratio from HME data) were prepared using a B-290 Spray Dryer (Buchi, Switzerland). Samples equivalent to 300 mg of IZD were added to 100 mL KCl (10 mmol) solution at 37 ◦ C, gently stirred, assessed by UV at predetermined timings, and finally analysed using TS-5000Z (Insent Inc., Atsugi-shi, Japan). Results: SLP and EPO based extrudates of IZD with varying loadings were successfully prepared by HME. In particular, 20% w/w showed the optimum taste masking effect with both polymers. Hence it was selected in the further study on process effect. With both processes, EPO exhibited better taste masking efficiency compared to SLP under different mechanisms; the better effect with HME may be explained by its significantly slower drug release while the SD system showed fast release (75% after 1 min) hence its better taste masking effect may result from drug-polymer interactions, which is still being investigated. Conclusions: Taste masking effect varies significantly with polymer and process. EPO shows better effect than SLP regardless of process applied although different mechanisms may apply. In contrast, the influence of process is more formulation dependent, with SD EPO/IZD (20/80, w/w) formulation showing the best effect among all systems studied. http://dx.doi.org/10.1016/j.ijpharm.2016.06.095 Abstract ID: 36 Designing and developing a medical device to facilitate dosing of free-flowing multiparticulates to the paediatric population Claire Jasmin Lewis 1,∗ , Joel Segal 2 , James McGovern 3 , Joanna Simmons 3 , Jonathan Burley 1 1
School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, UK 2 Faculty of Engineering, University of Nottingham, University Park, Nottingham NG7 2RD, UK 3 Pfizer Discovery Park, Sandwich, Kent CT13 9ND, UK Introduction: Multiparticulates are becoming an increasingly popular dosage form, their small size, improved taste masking ability and versatile nature compared to liquids and single unit counterparts lend themselves well to paediatric delivery. Coupling a multiparticulate drug delivery platform with a medical device will allow for the dosing flexibility required for administration to the whole paediatric age group. It is hoped this will fill a major gap in the market, as currently no administrative device is available capable of delivering a range of free-flowing multiparticulate doses. Purpose: To investigate means of flexibly dosing free-flowing material with a view to designing a novel medical device capable of administering multiparticulates to the paediatric population. Method: A number of existing devices, both volumetric and weight based, capable of handling free-flowing materials have been investigated to determine best practice for managing multiparticulate-like material. Precision and accuracy of the devices was investigated. Key user requirements were identified through stakeholder discussions and literature searching. Results: As part of early-stage designs for a paediatric multiparticulate dispenser, methods for achieving precise, accurate, reproducible and robust dosing have been investigated. A global user requirement specification has been developed. Conclusions: Early-stage design work has highlighted advantages of a weight based dispensing method. Further work will
Abstracts / International Journal of Pharmaceutics 511 (2016) 1127–1150
histone deacetylase (HDAC) inhibitor, was shown to significantly reduce fibrosis and promote compensatory muscle regeneration. Italfarmaco has developed a Givinostat oral liquid formulation being used as investigational medicinal product in the clinical study DSC/11/2357/43 (EudraCT no. 2012-002566-12) “A two parts study to assess the safety and tolerability, pharmacokinetics, and effects on histology and different clinical parameters of Givinostat in ambulant children with Duchenne Muscular Dystrophy”. This poster highlights the main development efforts leading to the obtainment of an acceptable oral liquid formulation for clinical development and the result of the assessment questionnaire on acceptability of the formulation submitted to children and parents during the course of the study. Method: API: Givinostat (as hydrochloride monohydrate) Excipients: compendial excipients Formulation development: based upon age appropriateness of formulation according to “Reflection Paper: Formulation of choice for the paediatric population” (EMEA/CHMP/PEG/194810/2005). Compliance (acceptability) of the formulation was assessed through a questionnaire submitted after 9 and 12 months of treatment during the course of the clinical study. Particularly children were requested to rank the taste of the formulation and parents to provide their feedback on both the taste and on the easiness of the administration procedure. Results and conclusions: Italfarmaco decided to develop an oral liquid formulation of Givinostat as oral liquid formulation is either ranked as “dosage form of choice” (children pre-school) or as “preferred acceptability” (children school and adolescents) in terms of acceptability. Italfarmaco has therefore developed a Givinostat oral liquid formulation allowing for an appropriate volume of administration (≥0.5 mL and ≤10 mL), wide dosage flexibility (that largely covers the anticipated doses for the clinical study) and an acceptable chemical stability at refrigerated conditions. Sweetening and flavouring agents (to cover the bitter taste and to give a basic sensation of sweet, see “Recommendation for selection and use of flavours in paediatric formulation, EMEA/CHMP/PEG/194810/2005) were added to possibly improve palatability characteristics. The results of the assessment questionnaire after 12 months treatment show an overall good acceptability of the developed formulation both in terms of taste and easiness of administration. The formulation can therefore be proposed for further clinical development. http://dx.doi.org/10.1016/j.ijpharm.2016.06.094 Abstract ID: 35 Taste masking of isoniazid by hot melt extrusion and spray drying – A comparative study Alison Keating, Duncan Craig, Catherine Tuleu, Claire Forbes, Barry Aldous, Min Zhao UCL School of Pharmacy, United Kingdom Introduction: Taste masked polymeric formulations have become increasingly popular in improving paediatric patient compliance. Hot melt extrusion (HME) is often recommended for producing such formulations while spray drying (SD) has not been extensively applied in this area. Hence it is of great significance to undertake a comparative study to investigate the different taste masking effects between the two processes. Purpose: To produce and compare polymeric formulations of isoniazid (IZD) by HME and SD for masking the bitter taste of IZD and understand the corresponding mechanisms. Method: Formulations of IZD with Soluplus (SLP) or Eudragit EPO (EPO) were prepared at a range of drug loadings by HME
(ThermoScientific, UK). Formulations at 20% drug loading (the most effective ratio from HME data) were prepared using a B-290 Spray Dryer (Buchi, Switzerland). Samples equivalent to 300 mg of IZD were added to 100 mL KCl (10 mmol) solution at 37 ◦ C, gently stirred, assessed by UV at predetermined timings, and finally analysed using TS-5000Z (Insent Inc., Atsugi-shi, Japan). Results: SLP and EPO based extrudates of IZD with varying loadings were successfully prepared by HME. In particular, 20% w/w showed the optimum taste masking effect with both polymers. Hence it was selected in the further study on process effect. With both processes, EPO exhibited better taste masking efficiency compared to SLP under different mechanisms; the better effect with HME may be explained by its significantly slower drug release while the SD system showed fast release (75% after 1 min) hence its better taste masking effect may result from drug-polymer interactions, which is still being investigated. Conclusions: Taste masking effect varies significantly with polymer and process. EPO shows better effect than SLP regardless of process applied although different mechanisms may apply. In contrast, the influence of process is more formulation dependent, with SD EPO/IZD (20/80, w/w) formulation showing the best effect among all systems studied. http://dx.doi.org/10.1016/j.ijpharm.2016.06.095 Abstract ID: 36 Designing and developing a medical device to facilitate dosing of free-flowing multiparticulates to the paediatric population Claire Jasmin Lewis 1,∗ , Joel Segal 2 , James McGovern 3 , Joanna Simmons 3 , Jonathan Burley 1 1
School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, UK 2 Faculty of Engineering, University of Nottingham, University Park, Nottingham NG7 2RD, UK 3 Pfizer Discovery Park, Sandwich, Kent CT13 9ND, UK Introduction: Multiparticulates are becoming an increasingly popular dosage form, their small size, improved taste masking ability and versatile nature compared to liquids and single unit counterparts lend themselves well to paediatric delivery. Coupling a multiparticulate drug delivery platform with a medical device will allow for the dosing flexibility required for administration to the whole paediatric age group. It is hoped this will fill a major gap in the market, as currently no administrative device is available capable of delivering a range of free-flowing multiparticulate doses. Purpose: To investigate means of flexibly dosing free-flowing material with a view to designing a novel medical device capable of administering multiparticulates to the paediatric population. Method: A number of existing devices, both volumetric and weight based, capable of handling free-flowing materials have been investigated to determine best practice for managing multiparticulate-like material. Precision and accuracy of the devices was investigated. Key user requirements were identified through stakeholder discussions and literature searching. Results: As part of early-stage designs for a paediatric multiparticulate dispenser, methods for achieving precise, accurate, reproducible and robust dosing have been investigated. A global user requirement specification has been developed. Conclusions: Early-stage design work has highlighted advantages of a weight based dispensing method. Further work will