An advanced automation platform coupled with mass spectrometry for investigating in vitro human skin permeation of UV filters and excipients in sunscreen products.

Rationale: Systemic absorption of UV-filtering chemicals following topical application of sunscreens may present a safety concern. The Food and Drug Administration (FDA) had recommended an in vitro skin permeation test (IVPT) to evaluate the potential of this safety risk for the evaluation of sunscreens prior to clinical studies. Therefore, a sensitive and robust bioanalytical method(s) were required for IVPT studies of different topical sunscreen products.

Identification of critical formulation parameters affecting the in vitro release, permeation, and rheological properties of the acyclovir topical cream.

To understand effects of formulation variables on the critical quality attributes (CQA) of acyclovir topical cream, this study investigated effects of propylene glycol (PG), poloxamer, and sodium lauryl sulfate (SLS) concentrations, acyclovir particle size, and formulation pH of the acyclovir cream. Fifteen formulations were prepared and characterized for rheological properties, particle size distribution, drug release and in vitro skin permeation. Drug distribution between various phases of the cream was determined.

In Vitro Testing of Sunscreens for Dermal Absorption: A Platform for Product Selection for Maximal Usage Clinical Trials.

Sunscreen products contain UV filters as active ingredients for the protection of the skin against UVR. The US Food and Drug Administration (FDA) issued a new proposed rule in 2019 (84.FR.

Formulation and characterization of curcumin loaded polymeric micelles produced via continuous processing.

A continuous processing platform was developed to produce polymeric micelles. A block copolymer of mPEG (5kD)-PCL (2kD) was used as the model drug carrier. The polymeric micelles were produced using an innovative co-axial turbulent jet with co-flow continuous technology to precisely control the physicochemical properties of the micelles.

Drug recrystallization in drug-in-adhesive transdermal delivery system: A case study of deteriorating the mechanical and rheological characteristics of testosterone TDS.

This study investigated the effects of drug recrystallization on the in vitro performance of testosterone drug-in-adhesive transdermal delivery system (TDS). Six formulations were prepared with a range of dry drug loading in the adhesive matrix from 1% to 10% w/w with the aim of generating TDS with various levels of drug crystals. We visually quantified the amount of crystals in TDS by polarized light microscopy.

Assessing Drug Release from Manipulated Abuse Deterrent Formulations.

There is a need to develop in vitro dissolution methods that discriminate for particle size of the manipulated abuse deterrent formulation (ADF) and that can be used for in vivo predictive models since dissolution methods developed for intact formulation might not be suitable for manipulated ones. A vertical diffusion cell (VDC) and United States Pharmacopeia (USP) Apparatus 1, 2, and 4 were evaluated for measuring the dissolution of intact and manipulated metoprolol succinate tablets with abuse deterrent-like properties. These tablets were physically manipulated to produce fine (106-500 μm) and coarse (500-1000 μm) powder samples.

Zinc supplementation improves the harvest purity of β-glucuronidase from CHO cell culture by suppressing apoptosis.

The variability of trace metals in cell culture media is a potential manufacturing concern because it may significantly affect the production and quality of therapeutic proteins. Variability in trace metals in CHO cell culture has been shown to impact critical production metrics such as cell growth, viability, nutrient consumption, and production of recombinant proteins. To better understand the influence of excess supplementation, zinc and copper were initially supplemented with 50-μM concentrations to determine the impact on the production and quality of β-glucuronidase, a lysosomal enzyme, in a parallel bioreactor system.

Evaluation of commercially available meth-deterrent pseudoephedrine hydrochloride products.

Pseudoephedrine (PSE) extracted from its dosage forms can be used as the starting material to prepare methamphetamine by drug abusers. Recently, some pseudoephedrine drug products marketed under the over the counter (OTC) monograph have been promoted as 'meth-deterrent'. The goal of this investigation was to evaluate the extraction and dissolution of these product against controls of non-meth-deterrent products of pseudoephedrine.

Understanding drug distribution and release in ophthalmic emulsions through quantitative evaluation of formulation-associated variables.

Establishing bioequivalence (BE) of ophthalmic emulsions in the absence of in vivo data is challenging. In these emulsions, drug release is a complex process due to drug distribution among various phases which are difficult to characterize. The objective of this study is to investigate the process of drug distribution and mechanism of drug release in the context of formulation-associated variables.

Development and applications of a material library for pharmaceutical continuous manufacturing of solid dosage forms.

The purpose of this study is to establish a material library and discuss its potential application to the development and lifecycle management of a continuous manufacturing process for solid dosage forms. Particularly, this study addresses the importance of selecting process-relevant testing conditions for material characterization, proposes a methodology to capture relevant information with a reduced set of measurements, and correlates material properties with process performance. This study included 20 pharmaceutical materials, and each material was characterized by 44 properties, capturing 880 data points.

Quality attributes and evaluation of pharmaceutical glass containers for parenterals.

Pharmaceutical containers for parenterals have been predominantly manufactured using glass as a packaging material of choice, especially Type-I glass, since it has been regarded as a chemically inert and an effective container closure system (CCS). Nevertheless, there have been reports and recalls related to glass quality issues, such as breakage, flakes, and particles observed in marketed products. The novelty of this research is based on the knowledge gathered from our previously conducted risk assessments and establishing a comprehensive testing platform focused on risk factors for glass container failure modes and applicability to other types of pharmaceutical containers.

A Kinetic Approach to Determining Drug Distribution in Complex Biphasic Systems.

Pharmaceutical emulsions contain multiple components, such as micellar, aqueous, and oil phases, leading to complex drug transfer and equilibrium phenomena. These complex components present challenges for the bioequivalence assessment of the drug products. The objective of the study was to develop a method that can probe the underlying mechanism and process of drug distribution.

Development of mechanistic models to identify critical formulation and process variables of pastes for 3D printing of modified release tablets.

The future of pharmaceutical manufacturing may be significantly transformed by 3-dimensional (3D) printing. As an emerging technology, the indicators of quality for materials and processes used in 3D printing have not been fully established. The objective of this study was to identify the critical material attributes of semisolid paste formulations filled into cartridges for 3D printing of personalized medicine.

Extrudability analysis of drug loaded pastes for 3D printing of modified release tablets.

The rheological characteristics of pastes for 3D printing of tablets may not be described fully by the traditional rheological tests generally used for other pastes. In the present study, extrudability testing of carbopol based 3D printing pastes was performed to establish a constitutive rheological model for micro-extrusion. This model was developed for pastes that exhibit a non-linear plasto-viscoelastic behavior and follow the generalized Herschel-Bulkley flow rule.

Application of in vitro lipolysis for the development of oral self-emulsified delivery system of nimodipine.

The objective of the current study was to optimize for the first time the formulation variables of self-emulsified drug delivery system (SEDDS) based on drug solubilization during lipolysis under a biorelevant condition of digestion such as lipase activity, temperature, pH, fed-fasting state, etc. Nimodipine (ND), a BCS class II, was used as a model drug to prepare the SEDDS. Various oils, surfactants, and cosurfactants were screened for their solubilization potential of ND.

Analytical considerations for measuring the globule size distribution of cyclosporine ophthalmic emulsions.

Measurement of particle size and size distribution of complex drug products exhibiting complex rheological behaviors can be challenging as these properties may be beyond the theoretical assumptions of the measurement technique. Herein cyclosporine (CsA) ophthalmic emulsion was selected as a model complex system, and an in-depth assessment of particle size was performed using five fundamentally different particle sizing techniques, including dynamic light scattering (DLS), laser diffraction (LD), nanoparticle tracking analysis (NTA), cryogenic transmission electron microscopy (Cryo-TEM) and 2-dimensional diffusion ordered spectroscopy nuclear magnetic resonance (2D DOSY-NMR). The effect of various viscosity modifying and stabilizing excipients in the emulsions was assessed using four types of CsA formulations, i.

Formulation characteristics and in vitro release testing of cyclosporine ophthalmic ointments.

The aim of the present study was to investigate the relationship between formulation/process variables versus the critical quality attributes (CQAs) of cyclosporine ophthalmic ointments and to explore the feasibility of using an in vitro approach to assess product sameness. A definitive screening design (DSD) was used to evaluate the impact of formulation and process variables. The formulation variables included drug percentage, percentage of corn oil and lanolin alcohol.

Asymmetric flow field flow fractionation for the characterization of globule size distribution in complex formulations: A cyclosporine ophthalmic emulsion case.

Commonly used characterization techniques such as cryogenic-transmission electron microscopy (cryo-TEM) and batch-mode dynamic light scattering (DLS) are either time consuming or unable to offer high resolution to discern the poly-dispersity of complex drug products like cyclosporine ophthalmic emulsions. Here, a size-based separation and characterization method for globule size distribution using an asymmetric flow field flow fractionation (AF4) is reported for comparative assessment of cyclosporine ophthalmic emulsion drug products (model formulation) with a wide size span and poly-dispersity. Cyclosporine emulsion formulations that are qualitatively (Q1) and quantitatively (Q2) the same as Restasis® were prepared in house with varying manufacturing processes and analyzed using the optimized AF4 method.

Application of Optical Coherence Tomography Freeze-Drying Microscopy for Designing Lyophilization Process and Its Impact on Process Efficiency and Product Quality.

Optical coherence tomography freeze-drying microscopy (OCT-FDM) is a novel technique that allows the three-dimensional imaging of a drug product during the entire lyophilization process. OCT-FDM consists of a single-vial freeze dryer (SVFD) affixed with an optical coherence tomography (OCT) imaging system. Unlike the conventional techniques, such as modulated differential scanning calorimetry (mDSC) and light transmission freeze-drying microscopy, used for predicting the product collapse temperature (Tc), the OCT-FDM approach seeks to mimic the actual product and process conditions during the lyophilization process.

Quality by Design approach for studying the impact of formulation and process variables on product quality of oral disintegrating films.

The present investigation was carried out to understand the impact of formulation and process variables on the quality of oral disintegrating films (ODF) using Quality by Design (QbD) approach. Lamotrigine (LMT) was used as a model drug. Formulation variable was plasticizer to film former ratio and process variables were drying temperature, air flow rate in the drying chamber, drying time and wet coat thickness of the film.

The evolving landscape of drug products containing nanomaterials in the United States.

The Center for Drug Evaluation and Research (CDER) within the US Food and Drug Administration (FDA) is tracking the use of nanotechnology in drug products by building and interrogating a technical profile of products containing nanomaterials submitted to CDER. In this Analysis, data from more than 350 products show an increase in the submissions of drug products containing nanomaterials over the last two decades. Of these, 65% are investigational new drugs, 17% are new drug applications and 18% are abbreviated new drug applications, with the largest class of products being liposomal formulations intended for cancer treatments.

How Has CDER Prepared for the Nano Revolution? A Review of Risk Assessment, Regulatory Research, and Guidance Activities.

The Nanotechnology Risk Assessment Working Group in the Center for Drug Evaluation and Research (CDER) within the United States Food and Drug Administration (FDA) was established to assess the potential impact of nanotechnology on drug products. One of the working group's major initiatives has been to conduct a comprehensive risk management exercise regarding the potential impact of nanomaterial pharmaceutical ingredients and excipients on drug product quality, safety, and efficacy. This exercise concluded that current review practices and regulatory guidance are capable of detecting and managing the potential risks to quality, safety, and efficacy when a drug product incorporates a nanomaterial.

Effect of Isopropyl Myristate on Transdermal Permeation of Testosterone From Carbopol Gel.

The objective of the present study was to investigate the effect of isopropyl myristate (IPM) on the in vitro permeation of testosterone through human cadaver skin from carbopol gels. Six testosterone gel formulations were prepared using different IPM contents of 0%, 0.4%, 0.

Product quality for nanomaterials: current U.S. experience and perspective.

In recent years, there has been an increased focus on developing novel drug delivery systems and targeted therapies through the use of nanotechnology and nanomaterials. Such focus is translating to an increasing number of investigational new drug (IND) applications, new drug applications (NDAs), and abbreviated new drug applications (ANDAs) for drug products containing nanomaterials to the United States Food and Drug Administration (FDA). Although subject to the same rigorous regulatory standards and regulatory pathways as any drug product, unique properties that arise from the small size, large surface area, and polydispersity of nanomaterials may lead to additional scientific considerations when following current FDA guidelines and practices for drug evaluation.