Novel Application of Hot Melt Extrusion for the Manufacturing of Vaginal Films Containing Microbicide Candidate Dapivirine

Regev, Galit; Patel, Sravan Kumar; Moncla, Bernard J.; Twist, John; Devlin, Bríd; Rohan, Lisa C.

doi:10.1208/s12249-019-1442-8

Cited by 21 publications

(8 citation statements)

References 26 publications

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“…Their portability is an important consideration for global distribution. Due to these advantages, multiple anti-retroviral drugs including DPV have been successfully formulated into polymeric films as topical microbicides for HIV prevention [18][19][20][21][22]. Their user acceptability, safety, pharmacokinetics, (PK) and pharmacodynamics (PD) (ex vivo challenge) have been evaluated in clinical studies [21,23,24].…”

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confidence: 99%

Rational Design of a Multipurpose Bioadhesive Vaginal Film for Co-Delivery of Dapivirine and Levonorgestrel

Regev

Patel

et al. 2019

Pharmaceutics

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Human immunodeficiency virus (HIV) infection and unintended pregnancy, which can lead to life-threatening complications, are two major burdens for female reproductive health. To address these pressing health issues, multipurpose prevention technologies (MPTs) are proposed to deliver two or more drugs simultaneously. MPTs could offer several benefits for users such as improved convenience, increased effectiveness, reduced cost, and decreased environmental burden. Here, we report the development, and in vitro and in vivo assessment of a bioadhesive vaginal film as a coitally-independent MPT dosage form for delivering dapivirine (DPV) and levonorgestrel (LNG) to prevent HIV infection and unintended pregnancy, respectively. After confirming the feasibility of bioadhesive film use for weekly drug delivery in vivo through colpophotography and MRI evaluation, the pharmacokinetics (PK) of DPV/LNG single entity and combination bioadhesive films was investigated in pigtailed macaques (n = 5). Both drugs from single entity or combination films were able to provide sustained drug release in vivo. The combination film showed lower local tissue clearance for DPV and exhibited significantly increased plasma concentration for LNG as compared to the single entity film. This proof-of-concept study demonstrates the ability of this novel bioadhesive film platform to deliver LNG and DPV simultaneously as an MPT product for the prevention of HIV infection and unintended pregnancy.

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confidence: 99%

Rational Design of a Multipurpose Bioadhesive Vaginal Film for Co-Delivery of Dapivirine and Levonorgestrel

Regev

Patel

et al. 2019

Pharmaceutics

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“…As an alternative formulation to solids and semi-solids, researchers used hot melt extrusion to manufacture a dapivirine vaginal film [ 72 ]. In another study, polymeric films were developed for the vaginal delivery of the highly potent and non-toxic, dual-acting HIV non-nucleoside reverse transcriptase inhibitor (NNRTI) pyrimidinedione, IQP-0528.…”

Section: Excipients Used In Modified Drug Release Pharmaceutical Dosage Forms For Vaginal Administrationmentioning

confidence: 99%

Recent Advances in the Excipients Used in Modified Release Vaginal Formulations

et al. 2022

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The formulation of an ideal vaginal drug delivery system (DDS), with the requisite properties, with respect to safety, efficacy, patient compliance, aesthetics, harmonization with the regulatory requirements, and cost, requires a meticulous selection of the active ingredients and the excipients used. Novel excipients defined by diversity and multifunctionality are used in order to ameliorate drug delivery attributes. Synthetic and natural polymers are broadly used in pharmaceutical vaginal formulations (solid, semi-solid dosage forms, implantable devices, and nanomedicines) with a promising perspective in improving stability and compatibility issues when administered topically or systemically. Moreover, the use of biopolymers is aiming towards formulating novel bioactive, biocompatible, and biodegradable DDSs with a controllable drug release rate. Overviewing vaginal microenvironment, which is described by variable and perplexed features, a perceptive choice of excipients is essential. This review summarizes the recent advances on the excipients used in modified vaginal drug delivery formulations, in an attempt to aid the formulation scientist in selecting the optimal excipients for the preparation of vaginal products.

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“…More recently, Regev et al developed microbicidal vaginal films containing dapivirine using the hot-melt extrusion (HME) technique while using a quality-by-design (QbD) approach [283]. When compared with solvent cast (SC) films of similar compositions, it was found that the HME films were thicker, heavier, had lower water content, and disintegrated faster than SC films while still being within acceptable attribute ranges for vaginal films.…”

Section: Vaginal Filmsmentioning

confidence: 99%

Recent Advances in Polymer-Based Vaginal Drug Delivery Systems

et al. 2021

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The vagina has been considered a potential drug administration route for centuries. Most of the currently marketed and investigated vaginal formulations are composed with the use of natural or synthetic polymers having different functions in the product. The vaginal route is usually investigated as an administration site for topically acting active ingredients; however, the anatomical and physiological features of the vagina make it suitable also for drug systemic absorption. In this review, the most important natural and synthetic polymers used in vaginal products are summarized and described, with special attention paid to the properties important in terms of vaginal application. Moreover, the current knowledge on the commonly applied and innovative dosage forms designed for vaginal administration was presented. The aim of this work was to highlight the most recent research directions and indicate challenges related to vaginal drug administrations. As revealed in the literature overview, intravaginal products still gain enormous scientific attention, and novel polymers and formulations are still explored. However, there are research areas that require more extensive studies in order to provide the safety of novel vaginal products.

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Novel Application of Hot Melt Extrusion for the Manufacturing of Vaginal Films Containing Microbicide Candidate Dapivirine

Cited by 21 publications

References 26 publications

Rational Design of a Multipurpose Bioadhesive Vaginal Film for Co-Delivery of Dapivirine and Levonorgestrel

Rational Design of a Multipurpose Bioadhesive Vaginal Film for Co-Delivery of Dapivirine and Levonorgestrel

Recent Advances in the Excipients Used in Modified Release Vaginal Formulations

Recent Advances in Polymer-Based Vaginal Drug Delivery Systems

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