Sacubitril-valsartan cocrystal revisited: role of polymer excipients in the formulation

Zhang, Yingxi; Du, Xiaoxiao; Wang, Hanxun; Zhang, He; Liu, Hongzhuo

doi:10.1080/17425247.2021.1860940

Cited by 16 publications

(18 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To develop a suitable cocrystal formulation, it is essential to check the physical stability of the cocrystal in the presence of excipients. The unintended dissociation of the cocrystal in the presence of excipients can lead to major formulation challenges and negate the potential benefits of cocrystals. , Therefore, information on cocrystal–excipient interactions is required for developing cocrystal formulations. The excipient compatibility of the PFD-FA cocrystal was studied with excipients used in the reference formulation (PIRFENEX, 200 mg) as well as test formulations, i.e., MCC, CCS, Aerosil, polyvinylpyrrolidone (PVP-K30), and magnesium stearate (MgSt) in a 1:1 (w/w) ratio as physical mixtures.…”

Section: Methodsmentioning

confidence: 99%

Investigating the Role of the Reduced Solubility of the Pirfenidone–Fumaric Acid Cocrystal in Sustaining the Release Rate from Its Tablet Dosage Form by Conducting Comparative Bioavailability Study in Healthy Human Volunteers

Kumari

Roy

Roy³

et al. 2022

Mol. Pharmaceutics

View full text Add to dashboard Cite

Pirfenidone (PFD) is the first pharmacological agent approved by the US Food and Drug Administration (FDA) in 2014 for the treatment of idiopathic pulmonary fibrosis (IPF). The recommended daily dosage of PFD in patients with IPF is very high (2403 mg/day) and must be mitigated through additives. In the present work, sustained-release (SR) formulations of the PFD-FA cocrystal of two different strengths such as 200 and 600 mg were prepared and its comparative bioavailability in healthy human volunteers was studied against the reference formulation PIRFENEX (200 mg). A single-dose pharmacokinetic study (200 mg IR vs 200 mg SR) demonstrated that the test formulation exhibited lower C max and T max in comparison to the reference formulation, which showed that the cocrystal behaved like an SR formulation. Further in the multiple-dose comparative bioavailability study (200 mg IR thrice daily vs 600 mg SR once daily), the test formulation was found bioequivalent to the reference formulation. In conclusion, the present study suggests that cocrystallization offers a promising strategy to reduce the solubility of PFD and opens the door for potential new dosage forms of this important pharmaceutical.

show abstract

Section: Methodsmentioning

confidence: 99%

Investigating the Role of the Reduced Solubility of the Pirfenidone–Fumaric Acid Cocrystal in Sustaining the Release Rate from Its Tablet Dosage Form by Conducting Comparative Bioavailability Study in Healthy Human Volunteers

Kumari

Roy

Roy³

et al. 2022

Mol. Pharmaceutics

View full text Add to dashboard Cite

show abstract

“…101 However, because of high hygroscopicity, film coating has been utilized in the formulation of the Entresto tablet. 102 Another interesting case of marketed pharmaceutical cocrystals is valproic acid/valproate sodium/water (1:3:1). In this case, formation of a salt cocrystal hydrate solved the high hygroscopicity of sodium valproate and the liquid state and the low solubility of the valproic acid.…”

Section: Implications Of Water Sorption By Cocrystalsmentioning

confidence: 99%

“…The salt cocrystal hydrate offers a 40% higher bioavailability of valsartan than valsartan given alone . However, because of high hygroscopicity, film coating has been utilized in the formulation of the Entresto tablet . Another interesting case of marketed pharmaceutical cocrystals is valproic acid/valproate sodium/water (1:3:1).…”

Section: Implications Of Water Sorption By Cocrystalsmentioning

confidence: 99%

Solid-State Interaction of Pharmaceutical Cocrystals with Water Vapor

Emami

Ghafari

Manafzadeh

2021

Crystal Growth & Design

View full text Add to dashboard Cite

The solid-state properties of an active pharmaceutical ingredient (API) largely determine the effectiveness of drug delivery to the patient. Solid APIs may be exposed to water during manufacturing and storage in an atmosphere containing water vapor. Moisture associated with APIs greatly influences their physicochemical properties such as chemical stability, interactions with excipients, and dissolution. Cocrystal formation with an appropriate coformer can improve solid-state properties of APIs such as chemical stability, photostability, solubility, and bioavailability. Moisture stability of APIs can be enhanced, deteriorated, or remain unchanged by cocrystal formation. Improving solid-state stability, especially against humidity, seems to be one of the most promising applications of cocrystals. Furthermore, to maintain the benefits achieved by cocrystals such as an enhanced dissolution rate, the cocrystals should preserve their structures through formulation, processing, and storage. The current review discusses different aspects of the interactions between pharmaceutical cocrystals and water vapor. First, we provide background information about hygroscopicity, the mechanism of interaction of water molecules with solids, and conventional methods for determining hygroscopicity. Then, the studies comparing the stability of cocrystals and parent APIs are presented. Finally, we discuss the consequences that may occur when a cocrystal interacts with water vapor including dissociation, hydration, polymorphic change, and interaction with excipients.

show abstract

“…Natriuretic peptides, including atrial, B-type, and C-type natriuretic peptides, are a group of polypeptides with a wide range of physiological effects, including the promotion of natriuresis and diuresis, vasodilation, RAAS inhibition, reduction of sympathetic nerve activity, and the suppression of proliferation and fibrosis ( 21 ). Sacubitril/valsartan, a compound with a co-crystal structure composed of the neprilysin inhibitor sacubitril and angiotensin receptor blocker valsartan, is the first dual angiotensin receptor and neprilysin inhibitor ( 22 , 23 ). Sacubitril is metabolized into LBQ657, which is an active metabolite that effectively inhibits neprilysin, thereby suppressing the neprilysin-mediated degradation of natriuretic peptides and enhancing the beneficial effect of the natriuretic peptide system.…”

Section: Introductionmentioning

confidence: 99%

Application of Angiotensin Receptor–Neprilysin Inhibitor in Chronic Kidney Disease Patients: Chinese Expert Consensus

Gan

Lyu²,

Yang³

et al. 2022

Front. Med.

View full text Add to dashboard Cite

Chronic kidney disease (CKD) is a global public health problem, and cardiovascular disease is the most common cause of death in patients with CKD. The incidence and prevalence of cardiovascular events during the early stages of CKD increases significantly with a decline in renal function. More than 50% of dialysis patients die from cardiovascular disease, including coronary heart disease, heart failure, arrhythmia, and sudden cardiac death. Therefore, developing effective methods to control risk factors and improve prognosis is the primary focus during the diagnosis and treatment of CKD. For example, the SPRINT study demonstrated that CKD drugs are effective in reducing cardiovascular and cerebrovascular events by controlling blood pressure. Uncontrolled blood pressure not only increases the risk of these events but also accelerates the progression of CKD. A co-crystal complex of sacubitril, which is a neprilysin inhibitor, and valsartan, which is an angiotensin receptor blockade, has the potential to be widely used against CKD. Sacubitril inhibits neprilysin, which further reduces the degradation of natriuretic peptides and enhances the beneficial effects of the natriuretic peptide system. In contrast, valsartan alone can block the angiotensin II-1 (AT1) receptor and therefore inhibit the renin–angiotensin–aldosterone system. These two components can act synergistically to relax blood vessels, prevent and reverse cardiovascular remodeling, and promote natriuresis. Recent studies have repeatedly confirmed that the first and so far the only angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril/valsartan can reduce blood pressure more effectively than renin–angiotensin system inhibitors and improve the prognosis of heart failure in patients with CKD. Here, we propose clinical recommendations based on an expert consensus to guide ARNI-based therapeutics and reduce the occurrence of cardiovascular events in patients with CKD.

show abstract

Sacubitril-valsartan cocrystal revisited: role of polymer excipients in the formulation

Cited by 16 publications

References 48 publications

Investigating the Role of the Reduced Solubility of the Pirfenidone–Fumaric Acid Cocrystal in Sustaining the Release Rate from Its Tablet Dosage Form by Conducting Comparative Bioavailability Study in Healthy Human Volunteers

Investigating the Role of the Reduced Solubility of the Pirfenidone–Fumaric Acid Cocrystal in Sustaining the Release Rate from Its Tablet Dosage Form by Conducting Comparative Bioavailability Study in Healthy Human Volunteers

Solid-State Interaction of Pharmaceutical Cocrystals with Water Vapor

Application of Angiotensin Receptor–Neprilysin Inhibitor in Chronic Kidney Disease Patients: Chinese Expert Consensus

Contact Info

Product

Resources

About