Fast Screening Methods for the Analysis of Topical Drug Products

Miranda, Margarida; Cardoso, Catarina; Vitorino, Carla

doi:10.3390/pr8040397

Cited by 7 publications

(5 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The microstructure and physical characterization of the formulations should include pH, rheological profile, polymorphism, API, and droplet size determination, together with a detailed understanding of both release kinetics and permeation behaviour [ 22 ].…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Complying with the Guideline for Quality and Equivalence for Topical Semisolid Products: The Case of Clotrimazole Cream

et al. 2021

View full text Add to dashboard Cite

Semisolids constitute a significant proportion of topical pharmaceutical dosage forms available on the market, with creams being considered profitable systems for releasing active substances into the skin. This work aimed at the development of a generic Clotrimazole topical cream, based on the assumptions that assist the development of such formulations. First, the critical parameters to obtain a final formulation as similar as possible to the reference product were defined. Then, the percentages of cetyl palmitate and octyldodecanol were identified as critical variables and chosen for optimization in further studies. A “quality by design” approach was then used to identify the effect of process variability on the structural and functional similarity (Q3) of the generic product qualitatively (Q1) and quantitatively (Q2). A two-factor central composite orthogonal design was applied and eleven different formulations were developed and subjected to physicochemical characterization and product performance studies. The results were used to estimate the influence of the two variables in the variation of the responses, and to determine the optimum point of the tested factors, using a design space approach. Finally, an optimized formulation was obtained and analysed in parallel with the reference. The obtained results agreed with the prediction of the chemometric analysis, validating the reliability of the developed multivariate models. The in vitro release and permeation results were similar for the reference and the generic formulations, supporting the importance of interplaying microstructure properties with product performance and stability. Lastly, based on quality targets and response constraints, optimal working conditions were successfully achieved.

show abstract

Section: Resultsmentioning

confidence: 99%

“…Design space is a multidimensional combination and interaction between the independent variables that assure quality. Working within the DS is not considered a change, since different experimental conditions may produce the same qualified product [ 22 , 44 ].…”

Section: Resultsmentioning

confidence: 99%

Complying with the Guideline for Quality and Equivalence for Topical Semisolid Products: The Case of Clotrimazole Cream

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Although not a direct indication of drug bioavailability, an in vitro release test (IVRT), using diffusion cells and synthetic membranes, can discriminate the differences in drug release rates arising from the formulation changes and various physicochemical properties of the semisolid drug products and consequently, can signal inadequate in vivo performances [ 35 ]. Hence, IVRT has been recognized as a valuable tool at various stages of the generic topical product development (early formulation development phase, scale-up, batch-to-batch consistency, life cycle management, post authorization changes) [ 36 , 37 ]. As a result, EMA draft guideline define the release rate as a CQA to be specified in the finished product release and shelf-life specification (unless otherwise justified).…”

Section: Demonstration Of Extended Pharmaceutical Equivalence Of Topical Semisolid Drug Productsmentioning

confidence: 99%

“…For this purpose, the investigation of drug solubility in different receptor media should first be performed. Considering that this step can be quite time consuming, recently, in silico studies using Chemaxon ® software (ChemAxon, Budapest, Hungary) were suggested to rationalize the selection of solvents suitable for solubility studies, based on respective chemical descriptors (such as size, geometry, lipophilicity, solubility, and surface topology) arising from drug chemical structure [ 37 ]. According to the EMA draft guideline, the duration of IVRT should be sufficient to properly characterize the release profile.…”

Section: Demonstration Of Extended Pharmaceutical Equivalence Of Topical Semisolid Drug Productsmentioning

confidence: 99%

“…Subsequently, hundreds of samples are generated throughout IVRT studies, requiring rapid analysis of drug content to avoid stability issues. In this sense, aiming to assist manufacturers of generic topical semisolid products, Miranda et al [ 37 ] recently established a portfolio of reversed-phase high-performance liquid chromatography (RP-HPLC) methods specifically tailored for commercially available topical products for a real-time drug analysis of the samples generated during the IVRT.…”

Section: Demonstration Of Extended Pharmaceutical Equivalence Of Topical Semisolid Drug Productsmentioning

confidence: 99%

See 1 more Smart Citation

The Implications of Regulatory Framework for Topical Semisolid Drug Products: From Critical Quality and Performance Attributes towards Establishing Bioequivalence

2021

View full text Add to dashboard Cite

Due to complex interdependent relationships affecting their microstructure, topical semisolid drug formulations face unique obstacles to the development of generics compared to other drug products. Traditionally, establishing bioequivalence is based on comparative clinical trials, which are expensive and often associated with high degrees of variability and low sensitivity in detecting formulation differences. To address this issue, leading regulatory agencies have aimed to advance guidelines relevant to topical generics, ultimately accepting different non-clinical, in vitro/in vivo surrogate methods for topical bioequivalence assessment. Unfortunately, according to both industry and academia stakeholders, these efforts are far from flawless, and often upsurge the potential for result variability and a number of other failure modes. This paper offers a comprehensive review of the literature focused on amending regulatory positions concerning the demonstration of (i) extended pharmaceutical equivalence and (ii) equivalence with respect to the efficacy of topical semisolids. The proposed corrective measures are disclosed and critically discussed, as they span from mere demands to widen the acceptance range (e.g., from ±10% to ±20%/±25% for rheology and in vitro release parameters highly prone to batch-to-batch variability) or reassess the optimal number of samples required to reach the desired statistical power, but also rely on specific data modeling or novel statistical approaches.

show abstract

Diving into Batch-to-Batch Variability of Topical Products-a Regulatory Bottleneck

Miranda

Cova

Augusto³

et al. 2020

Pharm Res

View full text Add to dashboard Cite

Fast Screening Methods for the Analysis of Topical Drug Products

Cited by 7 publications

References 32 publications

Complying with the Guideline for Quality and Equivalence for Topical Semisolid Products: The Case of Clotrimazole Cream

Complying with the Guideline for Quality and Equivalence for Topical Semisolid Products: The Case of Clotrimazole Cream

The Implications of Regulatory Framework for Topical Semisolid Drug Products: From Critical Quality and Performance Attributes towards Establishing Bioequivalence

Diving into Batch-to-Batch Variability of Topical Products-a Regulatory Bottleneck

Contact Info

Product

Resources

About