Co-extruded Fixed Dose Combination Products with Enabled Properties for the Treatment of Cardiovascular Diseases

Ammar Almajaan, Shu Li, Gareth C. Gilvary, Zoe Senta Loys, Yiwei Tian, Jeremiah Kelleher, Anne-Marie Healy, David Jones, Gavin Andrews

Research output: Contribution to conferencePaper

Abstract

Cardiovascular diseases (CVDs) are disorders associated with heart and blood vessels and are considered as the leading cause of morbidity and mortality worldwide (Bhatnagar 2015). The main risk factors associated with CVDs are smoking, hypertension and dyslipidaemia to mention few. Amongst them, dyslipidaemia is considered as the dominant risk factor (Yusuf 2001, Nelson 2013). Despite the fact that management of dyslipidaemia can be attained using different anti-hyperlipidemics such as statins, niacin, fibrates and bile acids, statins are considered as first line therapy (Whalen 2014). Simvastatin (SIM) is the most prescribed statin among others, nevertheless, due to its poor solubility and its susceptibility to metabolism by CYP 3A4, SIM is poorly bioavailable after oral administration (only 5% reaches the systemic circulation). Along with statins, long-term therapy with low-dose aspirin (ASP), is highly effective for the secondary prevention of cardiovascular (CV) events. The main concern associated with multiple therapy, however, is the poor adherence to medications. An efficient approach to overcome the poor adherence is by formulating multiple APIs into single dosage forms in fixed dose combinations (FDC). In this study, hot melt co-extrusion (HMCE) was used as a platform to manufacture a bi-layer concentric co-extrudate. These co-extrudates contain a FDC of ASP and (SIM) dispersed in the coat/core layers, respectively. The polymeric matrix of the coat is designed to release ASP immediately in the stomach, while the core layer is intended to release SIM in the proximal regions of the small intestine.
LanguageEnglish
DOIs
Publication statusPublished - 03 Apr 2019
EventAPS@FIP - Hilton Hotel, Glasgow, United Kingdom
Duration: 07 Sep 2018 → …

Conference

ConferenceAPS@FIP
CountryUnited Kingdom
CityGlasgow
Period07/09/2018 → …

Fingerprint

Hydroxymethylglutaryl-CoA Reductase Inhibitors
Simvastatin
Cardiovascular Diseases
Dyslipidemias
Aspirin
Fibric Acids
Medication Adherence
Niacin
Dosage Forms
Therapeutics
Secondary Prevention
Bile Acids and Salts
Solubility
Small Intestine
Blood Vessels
Oral Administration
Stomach
Smoking
Hypertension
Morbidity

Cite this

Almajaan, Ammar ; Li, Shu ; Gilvary, Gareth C. ; Senta Loys, Zoe ; Tian, Yiwei ; Kelleher, Jeremiah ; Healy, Anne-Marie ; Jones, David ; Andrews, Gavin. / Co-extruded Fixed Dose Combination Products with Enabled Properties for the Treatment of Cardiovascular Diseases. Paper presented at APS@FIP, Glasgow, United Kingdom.
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title = "Co-extruded Fixed Dose Combination Products with Enabled Properties for the Treatment of Cardiovascular Diseases",
abstract = "Cardiovascular diseases (CVDs) are disorders associated with heart and blood vessels and are considered as the leading cause of morbidity and mortality worldwide (Bhatnagar 2015). The main risk factors associated with CVDs are smoking, hypertension and dyslipidaemia to mention few. Amongst them, dyslipidaemia is considered as the dominant risk factor (Yusuf 2001, Nelson 2013). Despite the fact that management of dyslipidaemia can be attained using different anti-hyperlipidemics such as statins, niacin, fibrates and bile acids, statins are considered as first line therapy (Whalen 2014). Simvastatin (SIM) is the most prescribed statin among others, nevertheless, due to its poor solubility and its susceptibility to metabolism by CYP 3A4, SIM is poorly bioavailable after oral administration (only 5{\%} reaches the systemic circulation). Along with statins, long-term therapy with low-dose aspirin (ASP), is highly effective for the secondary prevention of cardiovascular (CV) events. The main concern associated with multiple therapy, however, is the poor adherence to medications. An efficient approach to overcome the poor adherence is by formulating multiple APIs into single dosage forms in fixed dose combinations (FDC). In this study, hot melt co-extrusion (HMCE) was used as a platform to manufacture a bi-layer concentric co-extrudate. These co-extrudates contain a FDC of ASP and (SIM) dispersed in the coat/core layers, respectively. The polymeric matrix of the coat is designed to release ASP immediately in the stomach, while the core layer is intended to release SIM in the proximal regions of the small intestine.",
author = "Ammar Almajaan and Shu Li and Gilvary, {Gareth C.} and {Senta Loys}, Zoe and Yiwei Tian and Jeremiah Kelleher and Anne-Marie Healy and David Jones and Gavin Andrews",
year = "2019",
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day = "3",
doi = "https://doi.org/10.5920/bjpharm.596",
language = "English",
note = "APS@FIP ; Conference date: 07-09-2018",

}

Co-extruded Fixed Dose Combination Products with Enabled Properties for the Treatment of Cardiovascular Diseases. / Almajaan, Ammar; Li, Shu; Gilvary, Gareth C.; Senta Loys, Zoe; Tian, Yiwei; Kelleher, Jeremiah; Healy, Anne-Marie; Jones, David; Andrews, Gavin.

2019. Paper presented at APS@FIP, Glasgow, United Kingdom.

Research output: Contribution to conferencePaper

TY - CONF

T1 - Co-extruded Fixed Dose Combination Products with Enabled Properties for the Treatment of Cardiovascular Diseases

AU - Almajaan, Ammar

AU - Li, Shu

AU - Gilvary, Gareth C.

AU - Senta Loys, Zoe

AU - Tian, Yiwei

AU - Kelleher, Jeremiah

AU - Healy, Anne-Marie

AU - Jones, David

AU - Andrews, Gavin

PY - 2019/4/3

Y1 - 2019/4/3

N2 - Cardiovascular diseases (CVDs) are disorders associated with heart and blood vessels and are considered as the leading cause of morbidity and mortality worldwide (Bhatnagar 2015). The main risk factors associated with CVDs are smoking, hypertension and dyslipidaemia to mention few. Amongst them, dyslipidaemia is considered as the dominant risk factor (Yusuf 2001, Nelson 2013). Despite the fact that management of dyslipidaemia can be attained using different anti-hyperlipidemics such as statins, niacin, fibrates and bile acids, statins are considered as first line therapy (Whalen 2014). Simvastatin (SIM) is the most prescribed statin among others, nevertheless, due to its poor solubility and its susceptibility to metabolism by CYP 3A4, SIM is poorly bioavailable after oral administration (only 5% reaches the systemic circulation). Along with statins, long-term therapy with low-dose aspirin (ASP), is highly effective for the secondary prevention of cardiovascular (CV) events. The main concern associated with multiple therapy, however, is the poor adherence to medications. An efficient approach to overcome the poor adherence is by formulating multiple APIs into single dosage forms in fixed dose combinations (FDC). In this study, hot melt co-extrusion (HMCE) was used as a platform to manufacture a bi-layer concentric co-extrudate. These co-extrudates contain a FDC of ASP and (SIM) dispersed in the coat/core layers, respectively. The polymeric matrix of the coat is designed to release ASP immediately in the stomach, while the core layer is intended to release SIM in the proximal regions of the small intestine.

AB - Cardiovascular diseases (CVDs) are disorders associated with heart and blood vessels and are considered as the leading cause of morbidity and mortality worldwide (Bhatnagar 2015). The main risk factors associated with CVDs are smoking, hypertension and dyslipidaemia to mention few. Amongst them, dyslipidaemia is considered as the dominant risk factor (Yusuf 2001, Nelson 2013). Despite the fact that management of dyslipidaemia can be attained using different anti-hyperlipidemics such as statins, niacin, fibrates and bile acids, statins are considered as first line therapy (Whalen 2014). Simvastatin (SIM) is the most prescribed statin among others, nevertheless, due to its poor solubility and its susceptibility to metabolism by CYP 3A4, SIM is poorly bioavailable after oral administration (only 5% reaches the systemic circulation). Along with statins, long-term therapy with low-dose aspirin (ASP), is highly effective for the secondary prevention of cardiovascular (CV) events. The main concern associated with multiple therapy, however, is the poor adherence to medications. An efficient approach to overcome the poor adherence is by formulating multiple APIs into single dosage forms in fixed dose combinations (FDC). In this study, hot melt co-extrusion (HMCE) was used as a platform to manufacture a bi-layer concentric co-extrudate. These co-extrudates contain a FDC of ASP and (SIM) dispersed in the coat/core layers, respectively. The polymeric matrix of the coat is designed to release ASP immediately in the stomach, while the core layer is intended to release SIM in the proximal regions of the small intestine.

U2 - https://doi.org/10.5920/bjpharm.596

DO - https://doi.org/10.5920/bjpharm.596

M3 - Paper

ER -