Interpretation and Optimization of the Dissolution Specifications for a Modified Release Product with an In Vivo–In Vitro Correlation (IVIVC)

Hayes, Siobhán; Dunne, Adrian; Smart, Trevor S.; Davis, John D.

doi:10.1002/jps.10552

Cited by 21 publications

(12 citation statements)

References 15 publications

(18 reference statements)

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“…The pharmaceutical industry primarily uses IVIVC for quality control, and most IVIVCs seek to mimic the dissolution of oral formulations in the gastrointestinal tract (22). In the present study, however, IVIVC was investigated in an attempt to establish a framework minimizing the number of in vivo studies required to reach the target drug levels.…”

Section: In Vivo Studies (I) Safety Profilesmentioning

confidence: 99%

Simultaneous Delivery of Tenofovir and Acyclovir via an Intravaginal Ring

Moss

Malone

Smith

et al. 2012

Antimicrob Agents Chemother

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Vaginal microbicides may play an important role in protecting women from HIV infection. A strong synergy between HSV and HIV has been observed, and epidemiological studies demonstrate that HSV infection increases the risk of HIV acquisition. Incorporation of the antiretroviral tenofovir (TFV) along with the antiherpetic acyclovir (ACV) into combination intravaginal rings (IVRs) for sustained mucosal delivery of both compounds could lead to increased microbicide product adherence and efficacy compared with conventional vaginal formulations. A novel, dual-protection "pod IVR" platform developed in-house and delivering ACV and TFV was evaluated in rabbit and sheep models. The devices were safe and exhibited sustained release of both drugs independently and at controlled rates over the 28-day studies. Daily release rates were estimated based on residual drug content of the used devices: rabbits, 343 ؎ 335 g day ؊1 (ACV) and 321 ؎ 207 g day ؊1 (TFV); sheep, 174 ؎ 14 g day ؊1 (ACV) and 185 ؎ 34 g day ؊1 (TFV). Mean drug levels in sheep vaginal samples were as follows: secretions, 5.25 ؎ 7.31 g ml ؊1 (ACV) and 20.6 ؎ 16.2 g ml ؊1 (TFV); cervicovaginal lavage fluid, 118 ؎ 113 ng ml ؊1 (ACV) and 191 ؎ 125 ng ml ؊1 (TFV); tissue, 173 ng g ؊1 (ACV) and 93 ng g ؊1 (TFV). An in vitro-in vivo correlation was established for both drugs and will allow the development of future formulations delivering target levels for prophylaxis and therapy. These data suggest that the IVR based on the pod design has potential in the prevention of transmission of HIV-1 and other sexually transmitted pathogens. Significant progress has been achieved in providing increased access to HIV/AIDS services in several low-and middleincome countries (44). Despite these encouraging findings, women in the developing world remain disproportionately at risk of HIV infection. Seventy-six percent of new HIV infections in sub-Saharan Africa occur in women aged 15 to 24 years (42). The proportion is as high as 90% in South Africa (38). In the absence of a preventative vaccine, effective prophylactic biomedical technologies are urgently required. Campaigns aimed at encouraging monogamy and condom use have had limited success in areas where marriage has been identified as the major risk factor for HIV acquisition in women (3,15,16,21,25).Human immunodeficiency virus type 1 (HIV-1) and herpes simplex virus type 2 (HSV-2), the serotype most commonly associated with genital herpes, are responsible for two intersecting epidemics, where the disease caused by one virus facilitates the transmission of and pathogenesis by the other. A strong synergy between HSV and HIV has been observed, and epidemiological studies demonstrate that HSV infection increases the risk of HIV-1 acquisition (33,34,43). A meta-analysis found that prevalent HSV-2 infection is associated with a threefold-increased risk of HIV acquisition among both men and women. These results suggest that, in areas of high HSV-2 prevalence, a substantial proportion of HIV infection is linked to HSV-2 infection (...

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Section: In Vivo Studies (I) Safety Profilesmentioning

confidence: 99%

Simultaneous Delivery of Tenofovir and Acyclovir via an Intravaginal Ring

Moss

Malone

Smith

et al. 2012

Antimicrob Agents Chemother

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“…Gillespie and VengPedersen (1985), Gillespie (1997), Dunne et al (1999), O'Hara et al (2001), and Hayes et al (2004) showed, based on in vitro dissolution data and in vivo immediate release plasma concentrations, that the slow release formulation concentrations can be predicted and an IVIVC established using a convolution-based method. This method is more robust than the deconvolution method (Dunne et al, 2005), and it jointly fits a set of models.…”

Section: In Vivo Modelsmentioning

confidence: 97%

“…Thus no expensive in vivo bioequivalence testing is required for either situation (Hayes et al, 2004). This technique can also be applied in formulation development.…”

Section: Introductionmentioning

confidence: 98%

Combined Models for Data from In Vitro–In Vivo Correlation Experiments

Jacobs

Rossenu

Dunne

et al. 2008

Journal of Biopharmaceutical Statistics

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A method is presented to describe the in vitro-in vivo correlation (IVIVC) of an extended release drug formulation. This extended release drug product is overencapsulated with immediate release material. The heterogeneity of the capsule is modelled using a combined model of an extended release and an immediate release pharmacokinetic profile. Whereas an IVIVC is conventionally performed using a two-stage procedure, the model uses a one-stage convolution-based method. The method is applied to a Galantamine controlled release formulation, an acetylcholinesterase inhibitor for the treatment of Alzheimer's disease. The average percentage prediction error indicated a good fit of the new model.

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“…In vitro in vivo correlation is established to facilitate dissolution test to be used as surrogacy for bio study and it benefit the pharmaceutical manufacturer in terms of time and cost on bioequivalence study. [7][8][9][10] In vitro in vivo correlation models will be useful for optimizing the SR (sustained release) dosage forms, otherwise predict in vivo performance of the SR dosage forms based on in vitro dissolution data. The FDA guidance has identified three In vitro in vivo correlation models: namely, level A, B, and C models.…”

Section: Introductionmentioning

confidence: 99%

“…6 Numerous investigations have been undertaken to develop In vitro in vivo correlation models, a level A correlation utilize the complete time course of in vitro dissolution and in vivo input and recognized model of choice for achieve biowaivers or setting of dissolution specifications. [7][8][9][10][11][12][13][14][15][16] However, level B and C models may be used in the initial stages of formulation development to inspect level A In vitro in vivo correlation models shall be used. 6 The present work aim was to develop and establish the internal and external predictability of level A In vitro in vivo correlation models for the three Metoclopramide sustained release and one immediate release formulation were evaluated.…”

Section: Introductionmentioning

confidence: 99%

Development and Evaluation of Internal and External Predictability of Metoclopramide Hydrochloride Modified Release Formulations: An Establishment of Level A In vitro and In vivo Correlation

Narayanasamy¹,

Shabaraya²

2017

IJPER

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The objective of this study was to develop an in vitro-in vivo correlation (IVIVC) model for hydrophilic matrix sustained-release (SR) Metoclopramide formulations. The in vitro release characteristics of the drug were determined using USP apparatus II at 50 rpm, pH 6.8. In vivo plasma concentrations and pharmacokinetic parameters in healthy human subjects were obtained after administering oral dose, developed SR formulations and marketed immediate-release (IR) products. The similarity factor f2 was used to compare the dissolution data. The IVIVC model was developed using pooled fraction dissolved and fraction absorbed of developed SR formulations i.e. fast, medium and slow release and marketed immediate-release (IR) products. An in vitro-in vivo correlation (IVIVC) was established for sustained release tablet by deconvolution using data from an immediate-release treatment as the characteristic response. To assess the correlation between in vitro dissolution uniqueness and in vivo absorption performance of Metoclopramide sustained release (SR) and immediate release (IR) tablet in human subjects. The established IVIVC was evaluated internally by predicting data used to develop and externally by predicting data not originally included in developing the IVIVC model. The observed low prediction errors for Cmax and AUC demonstrated that the Metoclopramide IVIVC model was valid.

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Interpretation and Optimization of the Dissolution Specifications for a Modified Release Product with an In Vivo–In Vitro Correlation (IVIVC)

Cited by 21 publications

References 15 publications

Simultaneous Delivery of Tenofovir and Acyclovir via an Intravaginal Ring

Simultaneous Delivery of Tenofovir and Acyclovir via an Intravaginal Ring

Combined Models for Data from In Vitro–In Vivo Correlation Experiments

Development and Evaluation of Internal and External Predictability of Metoclopramide Hydrochloride Modified Release Formulations: An Establishment of Level A In vitro and In vivo Correlation

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