Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Sitagliptin Phosphate Monohydrate

Charoo, Naseem A.; Abdallah, Daud Baraka; Bakheit, Ahmed Abdalla; Haque, Kashif Ul; Hassan, Hassan Ali; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Langguth, Peter; Mehta, Mehul; Parr, Alan; Polli, James E.; Shah, Vinod P.; Tajiri, Tomokazu; Dressman, Jennifer B.

doi:10.1016/j.xphs.2021.09.031

Cited by 7 publications

(2 citation statements)

References 41 publications

(57 reference statements)

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“…Sitagliptin phosphate monohydrate, a DPP-4 inhibitor, has a molecular weight of 523.32 g/mol, and has good solubility and permeability as its biopharmaceutics classification system (BCS) is Class 1. In addition, sitagliptin phosphate monohydrate has a time to maximum plasma concentration (Tmax) of 1 to 4 h and has a suitable distribution volume and rapid oral absorption in vivo with a bioavailability of approximately 87% [17]. Dapagliflozin propanediol hydrate ((1S)-1,5-Anhydro-1-C-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-D-glucitol (S)-propane-1,2-diol (1:1) monohydrate, BMS 512148 propanediol monohydrate, Dapagliflozin (S)-propylene glycol monohydrate, (2S,3R,4R,5S,6R)-2-(3-(4-Ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyl-tetrahydro-2H-pyran-3,4,5-triol propanediol monohydrate) is a type 2 oral antidiabetic drug that is a sodium-glucose cotransporter-2 (SGLT-2) inhibitor and reduces blood glucose independently of insulin action [18].…”

Section: Introductionmentioning

confidence: 99%

Development of Clinically Optimized Sitagliptin and Dapagliflozin Complex Tablets: Pre-Formulation, Formulation, and Human Bioequivalence Studies

Kang

Kim

2023

Pharmaceutics

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The purpose of this study is to derive an optimal drug release formulation with human clinical bioequivalence in developing a sitagliptin phosphate monohydrate-dapagliflozin propanediol hydrate fixed-dose combination (FDC) tablet as a treatment for type 2 diabetes mellitus. As a treatment for type 2 diabetes mellitus, the combined prescription of dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium-glucose cotransporter-2 (SGLT-2) inhibitors is common. Therefore, this study simplified the number of individual drugs taken and improved drug compliance by developing FDC tablets containing sitagliptin phosphate monohydrate as a DPP-4 inhibitor and dapagliflozin propanediol hydrate as an SGLT-2 inhibitor. To derive the optimal dosage form, we prepared single-layer tablets, double-layer tablets, and dry-coated tablets and evaluated the drug control release ability, tableting manufacturability, quality, and stability. Single-layer tablets caused problems with stability and drug dissolution patterns. When the dissolution test was performed on the dry-coated tablets, a corning effect occurred, and the core tablet did not completely disintegrate. However, in the quality evaluation of the double-layer tablets, the hardness was 12–14 kilopond, the friability was 0.2%, and the disintegration was within 3 min. In addition, the stability test revealed that the double-layer tablet was stable for 9 months under room temperature storage conditions and 6 months under accelerated storage conditions. In the drug release test, only the FDC double-layer tablet showed the optimal drug release pattern that satisfied each drug release rate. In addition, the FDC double-layer tablet showed a high dissolution rate of over 80% in the form of immediate-release tablets within 30 min in a pH 6.8 dissolution solution. In the human clinical trial, we co-administered a single dose of a sitagliptin phosphate monohydrate-dapagliflozin propanediol hydrate FDC double-layered tablet and the reference drug (Forxiga®, Januvia®) in healthy adult volunteers. This study showed clinically equivalent results in the stability and pharmacodynamic characteristics between the two groups.

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Section: Introductionmentioning

confidence: 99%

Development of Clinically Optimized Sitagliptin and Dapagliflozin Complex Tablets: Pre-Formulation, Formulation, and Human Bioequivalence Studies

Kang

Kim

2023

Pharmaceutics

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“…However, if the test product contains an unapproved drug substance or an unapproved drug substance ester, ether, isomer, mixture of isomers, complex, or derivative, the biowaiver cannot be used. Biowaivers based on BCS can be considered for pro-drugs that are absorbed in their pro-drug form (23).…”

Section: Introductionmentioning

confidence: 99%

BCS Class II Drug & Its Solubility Enhancement: A Review

Bajpai¹,

Singh²,

Bisht³

et al. 2022

J. Res. Appl. Sci. Biotechnol.

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The objective of this review article is to summarize literature data pertinent to potential excipient effects on intestinal drug permeability and transit. Despite the use of excipients in drug products for decades, considerable research efforts have been directed towards evaluating their potential effects on drug bioavailability. Potential excipient concerns stem from drug formulation changes (e.g., scale-up and post-approval changes, development of a new generic product). Regulatory agencies have established in vivo bioequivalence standards and, as a result, may waive the in vivo requirement, known as a biowaiver, for some oral products. Biowaiver acceptance criteria are based on the in vitro characterization of the drug substance and drug product using the Biopharmaceutics Classification System (BCS). Various regulatory guidance documents have been issued regarding BCS-based biowaivers, such that the current FDA guidance is more restrictive than prior guidance, specifically about excipient risk. In particular, sugar alcohols have been identified as potential absorption-modifying excipients. These biowaivers and excipient risks are discussed here.

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Biowaiver based on biopharmaceutics classification system: Considerations and requirements

Dhake,

Kumbhar,

Gaikwad

2024

Pharmaceutical Science Advances

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Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Sitagliptin Phosphate Monohydrate

Cited by 7 publications

References 41 publications

Development of Clinically Optimized Sitagliptin and Dapagliflozin Complex Tablets: Pre-Formulation, Formulation, and Human Bioequivalence Studies

Development of Clinically Optimized Sitagliptin and Dapagliflozin Complex Tablets: Pre-Formulation, Formulation, and Human Bioequivalence Studies

BCS Class II Drug & Its Solubility Enhancement: A Review

Biowaiver based on biopharmaceutics classification system: Considerations and requirements

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