Once‐a‐Day Controlled‐Release Dosage Form of Divalproex Sodium II: Development of a Predictive In Vitro Drug Release Method

Qiu, Yihong; Garren, J.; Samara, Emil; Cao, Guoliang; Abraham, C.; Cheskin, Howard; Engh, Kevin

doi:10.1002/jps.10486

Cited by 27 publications

(23 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consequently, a change in S/V ratio resulted in different release rates between the two strengths. The results of the current study indicate that in vitro multimedia dissolution testing is unable to discriminate between formulations with acceptable and unacceptable in vivo behavior of drug A ER tablets, which is consistent with previous studies involving formulations with different release rates during the development of IVIVC (26).…”

Section: Case Iii: Er Tablets Of Drug Csupporting

confidence: 87%

“…The in vitro results in multimedia differ significantly in both release rate and kinetics from the in vivo apparent absorption profiles obtained by deconvolution (1,26). Using the IVIVC-based test method, the proportionally similar strengths exhibited not only dissimilar profiles but also a more rapid and predominantly erosion-controlled release mechanism, consistent with the in vivo observation (Fig.…”

Section: Case Iii: Er Tablets Of Drug Csupporting

confidence: 72%

See 1 more Smart Citation

Influence of Drug Properties and Formulation on In Vitro Drug Release and Biowaiver Regulation of Oral Extended Release Dosage Forms

Lin

Zhou

Hoag

et al. 2016

AAPS J

Self Cite

View full text Add to dashboard Cite

Abstract. Bioequivalence (BE) studies are often required to ensure therapeutic equivalence for major product and manufacturing changes. Waiver of a BE study (biowaiver) is highly desired for such changes. Current regulatory guidelines allow for biowaiver of proportionally similar lower strengths of an extended release (ER) product provided it exhibits similar dissolution to the higher strength in multimedia. The objective of this study is to demonstrate that (1) proportionally similar strengths of ER tablets exhibiting similar in vitro dissolution profiles do not always assure BE and (2) different strengths that do not meet the criteria for dissolution profile similarity may still be bioequivalent. Four marketed ER tablets were used as model drug products. Higher and lower (half) strength tablets were prepared or obtained from commercial source. In vitro drug release was compared using multi-pH media (pH 1.2, 4.5, 6.8) per regulatory guidance. In vivo performance was assessed based on the available in vivo BE data or established in vitro-in vivo relationships. This study demonstrated that the relationship between in vitro dissolution and in vivo performance is complex and dependent on the characteristics of specific drug molecules, product design, and in vitro test conditions. As a result, proportionally similar strengths of ER dosage forms that meet biowaiver requirements per current regulatory guidelines cannot ensure bioequivalence in all cases. Thus, without an established relationship between in vitro and in vivo performance, granting biowaiver based on passing in vitro tests may result in the approval of certain bioinequivalent products, presenting risks to patients. To justify any biowaiver using in vitro test, it is essential to understand the effects of drug properties, formulation design, product characteristics, test method, and its in vivo relevance. Therefore, biowaiver requirements of different strengths of ER dosage forms specified in the current regulatory guidance should be reevaluated to assure consistent safety and efficacy among different strengths.KEY WORDS: bioequivalence; biowaiver; extended release; in vitro drug release; in vivo evaluations; proportionally similar strength.

show abstract

Section: Case Iii: Er Tablets Of Drug Csupporting

confidence: 87%

Section: Case Iii: Er Tablets Of Drug Csupporting

confidence: 72%

Influence of Drug Properties and Formulation on In Vitro Drug Release and Biowaiver Regulation of Oral Extended Release Dosage Forms

Lin

Zhou

Hoag

et al. 2016

AAPS J

Self Cite

View full text Add to dashboard Cite

show abstract

“…Briefly, USP apparatus II, operating at 100 rpm, was used as a dissolution tester, and the test was performed in 500 ml of 0.1 N HCl for 45 min as the acid stage, followed by 900 ml of 0.05 M phosphate buffer pH 5.5, containing 0.5% SLS as the buffer phase. Temperature was maintained at 37 ± 0.5°C (17). Samples was withdrawn at predetermined time intervals (15 and 45 min initially and 1, 2, 4, 6, 12, and 24 h thereafter).…”

Section: Dissolution Studiesmentioning

confidence: 99%

Design and Optimization of Sustained-Release Divalproex Sodium Tablets with Response Surface Methodology

et al. 2012

View full text Add to dashboard Cite

Abstract. Response surface methodology is defined as a collection of mathematical and statistical methods that are used to develop, improve, or optimize a product or process. In the present study, a statistical design (Mixture Design) was employed for formulation and optimization of a sustained-release hydrophilic divalproex sodium matrix tablet. Different excipients were used to improve the drug's poor flowability. The hardness of the prepared tablets and also their release pattern were tested. The formulation design was carried out employing mixture design using four excipients in three levels. The Carr's index of formulations and tensile strength were determined and analyzed using Minitab software. The suitable formulations regarding flowability and tablet tensile strength were selected by this software for subsequent drug release studies. The dissolution tests were carried out in acidic and basic phases which were previously proved to be biomimetic. Samples were analyzed using HPLC, and release data were compared to Depakine® (sustained-release divalproex from Sanofi). Release kinetics was also determined for selected formulations. Selected formulations were subjected to dissolution test and showed similar dissolution profiles with Depakine® based on difference and similarity factor calculations. The software selected an optimized formulation which had a slightly different release pattern in vitro compared to innovator but of nearly zero-order kinetics. It can be concluded that application of Mixture Design is a shortcut method to design suitable formulations of sustained-release divalproex sodium containing hydrophilic matrix tablets by direct compression method.

show abstract

“…The oral extended release dosage forms prove to be more beneficial than conventional dosage forms as they improve patient compliance and therapeutic efficacy by reducing the dosing frequency, prolonging therapeutic effect and enhancing the bioavailability. 12 However, the problem arises when a weakly basic drug is to be formulated as an extended release dosage form. The weakly basic drugs show high aqueous solubility at low pH values, but at higher pH, they precipitate within the formulation and are no longer released.…”

Section: Introductionmentioning

confidence: 99%

Matrix Tablet Containing Quaternary Inclusion Complex of Domperidone for Treatment of Diabetic Gastroparesis

Ghorpade¹,

Mali²,

Dias³

et al. 2017

IJPER

View full text Add to dashboard Cite

Objective: The present investigation is aimed at development and optimization of a pH independent controlled release matrix tablet containing mannitol based quaternary inclusion complex (QIC) of domperidone (DOM) for the treatment of diabetic gastroparesis. Methods: The tablets were prepared by direct compression and central composite design was used to optimize the amount of sodium alginate (SA) and hydroxypropylmethylcellulose (HPMC) to obtain a final formulation with desired release characteristics. The drug release from the optimized formulation was compared with the tablets containing pure DOM, binary and ternary inclusion complexes. Results and Discussion: The formulations showed a zero order release profile. The design models suggested greater influence of SA on the drug release. The optimized formulation showed minimum burst effect and released 88.65±3.19% DOM at the end of 12 h. The comparative study revealed that the optimized formulation exhibited nearly complete release of DOM. Conclusion: It was concluded that the optimized formulation containing QIC may reduce the dose frequency and improve the bioavailability of DOM.

show abstract

Once‐a‐Day Controlled‐Release Dosage Form of Divalproex Sodium II: Development of a Predictive In Vitro Drug Release Method

Cited by 27 publications

References 18 publications

Influence of Drug Properties and Formulation on In Vitro Drug Release and Biowaiver Regulation of Oral Extended Release Dosage Forms

Influence of Drug Properties and Formulation on In Vitro Drug Release and Biowaiver Regulation of Oral Extended Release Dosage Forms

Design and Optimization of Sustained-Release Divalproex Sodium Tablets with Response Surface Methodology

Matrix Tablet Containing Quaternary Inclusion Complex of Domperidone for Treatment of Diabetic Gastroparesis

Contact Info

Product

Resources

About