In and Beyond COVID-19: US Academic Pharmaceutical Science and Engineering Community Must Engage to Meet Critical National Needs.
Abstract The supply of affordable, high-quality pharmaceuticals to US patients has been on a critical path for decades. In and beyond the COVID-19 pandemic, this critical path has become tortuous. To regain reliability, reshoring of the pharmaceutical supply chain to the USA is now a vital national security need. Reshoring the pharmaceutical supply with old know-how and outdated technologies that cause inherent unpredictability and adverse environmental impact will neither provide the security we seek nor will it be competitive and affordable. The challenge at hand is complex akin to redesigning systems, including...
Source: AAPS PharmSciTech - May 24, 2020 Category: Drugs & Pharmacology Authors: Gurvich VJ, Hussain AS Tags: AAPS PharmSciTech Source Type: research

Proniosomal Microcarriers: Impact of Constituents on the Physicochemical Properties of Proniosomes as a New Approach to Enhance Inhalation Efficiency of Dry Powder Inhalers.
Abstract Proniosomes are free-flowing systems with coating carriers, which developed as a method for improving the drug flow and pulmonary delivery. Extensive research on proniosomes was done to enhance the dry powder inhalers (DPI)'s inhalation performance. This research aimed at studying the impact of lactose-mannitol mixture additives on the proniosome's physicochemical properties as a method for improving the inhalation efficiency of DPI. Vismodegib has been employed as a compound model. Box-Behnken design has been employed to prepare different proniosomes formulae by incorporating various (A) span 60 concentr...
Source: AAPS PharmSciTech - May 24, 2020 Category: Drugs & Pharmacology Authors: Gamal A, Saeed H, Sayed OM, Kharshoum RM, Salem HF Tags: AAPS PharmSciTech Source Type: research

Meloxicam Carrier Systems Having Enhanced Release and Aqueous Wettability Prepared Using Micro-suspensions in Different Liquid Media.
ný P Abstract One of the conventional methods of alleviating the problem of poor drug solubility is the particle size reduction. The efficiency of this approach depends on successful formulation suppressing the drug agglomeration. The aim of this study was to circumvent the dissolution problems of model hydrophobic meloxicam drug (MLX) by using liquid media of different wetting capacity to comminute and formulate a rapidly dissolving carrier system without the use of surfactants. Micro-suspensions of MLX were prepared by ball milling, using water or n-Heptane as a liquid medium. The suspensions were used as...
Source: AAPS PharmSciTech - May 24, 2020 Category: Drugs & Pharmacology Authors: Marinko N, Zámostný P Tags: AAPS PharmSciTech Source Type: research

Continuous Manufacturing of a Polymer Stabilized Emulsion Monitored with Process Analytical Technology.
Abstract Moving from batch to continuous manufacturing (CM) requires implementation of process analytical technology (PAT), as it is crucial to monitor and control these processes. CM of semi-solids has been demonstrated but implementation of a broader range of PAT tools with in- or on-line process interfacing at the end of the CM line has not been demonstrated. The goal of this work was to continuously manufacture creams and to investigate whether in- and on-line measurement of viscosity, changes in the concentration of active pharmaceutical ingredient (API), and pH could be used to support optimization of a mode...
Source: AAPS PharmSciTech - May 24, 2020 Category: Drugs & Pharmacology Authors: Qwist PK, Sander C, Bostijn N, Jessen V, Rantanen J, De Beer T Tags: AAPS PharmSciTech Source Type: research

Understanding Concomitant Physical and Chemical Transformations of Simvastatin During Dry Ball Milling.
Abstract The present study investigates concomitant processes of solid-state disordering and oxidation of simvastatin during milling. The separate dry ball milling of crystalline and amorphous powders of simvastatin were conducted at ambient temperature for 10 and 60 min each. The relative crystallinity was determined using X-ray scattering and oxidative degradation was analyzed using liquid chromatography. The physical and chemical transformations in the milled powder were evaluated using modulated differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy. The disordering during mil...
Source: AAPS PharmSciTech - May 21, 2020 Category: Drugs & Pharmacology Authors: Modhave D, Saraf I, Karn A, Paudel A Tags: AAPS PharmSciTech Source Type: research

EGFR Targeted Paclitaxel and Piperine Co-loaded Liposomes for the Treatment of Triple Negative Breast Cancer.
Abstract Triple-negative breast (TNBC) cancer that is upregulated with epidermal growth factor receptor (EGFR), and devoid of both the hormonal receptors and epidermal growth factor receptor 2 (HER 2), has led to a concept of treating TNBC with EGFR-targeted therapeutics. The combination of paclitaxel (PTX) and piperine (PIP) may improve the bioavailability of paclitaxel for cancer therapy. TPGS (vit E-PEG 1000-succinate)-coated liposomes were prepared with PTX alone or in combination with PIP, and either with (targeted) or without (non-targeted) cetuximab (CTX) conjugation. The Bradford assay indicated ...
Source: AAPS PharmSciTech - May 21, 2020 Category: Drugs & Pharmacology Authors: Burande AS, Viswanadh MK, Jha A, Mehata AK, Shaik A, Agrawal N, Poddar S, Mahto SK, Muthu MS Tags: AAPS PharmSciTech Source Type: research

Evaluation of the Sensitivity and Robustness of Modified Chi-Square Ratio Statistic for Cascade Impactor Equivalence Testing Through Monte Carlo Simulations.
In conclusion, the mCSRS test is a sensitive and robust method under most conditions. PMID: 32435854 [PubMed - in process] (Source: AAPS PharmSciTech)
Source: AAPS PharmSciTech - May 20, 2020 Category: Drugs & Pharmacology Authors: Kurumaddali A, Christopher D, Strickland H, Morgan B, Wiggenhorn C, Stein S, Lyapustina S, Hochhaus G Tags: AAPS PharmSciTech Source Type: research

Development of Morin-Loaded Nanoemulsions Containing Various Polymers; Role of Polymers in Formulation Properties and Bioavailability.
Abstract Emulsions for oral delivery are not suitable for sustained drug absorption because such preparations diffuse rapidly in the gastrointestinal (GI) tract after oral administration. In order to generate sustained drug absorption and increase oral bioavailability, various polymers were added to a morin (MO) nanoemulsion to improve retention in the GI tract and alter the surface properties of oil droplets in the nanoemulsion. The influence of these polymers on the formulation properties was investigated. The area under the blood concentration-time curve (AUC) and the mean residence time (MRT) after oral admini...
Source: AAPS PharmSciTech - May 20, 2020 Category: Drugs & Pharmacology Authors: Ikeuchi-Takahashi Y, Murata S, Murata W, Kobayashi A, Ishihara C, Onishi H Tags: AAPS PharmSciTech Source Type: research

Effect of Genotype and Sex of the Host on the Bioavailability of Novel Albendazole Microcrystals Based on Chitosan and Cellulose Derivatives.
Abstract Albendazole (ABZ), an anthelmintic compound widely used in the treatment of systemic nematode infections, is included in the list of class II drugs based on the Biopharmaceutical Classification System. ABZ has limited effectiveness due to its poor water solubility and consequent low bioavailability. Bioavailability of novel ABZ microcrystals based on hydroxyethylcellulose (S4A) or chitosan (S10A) was studied in male and female mice of two inbred lines, from the murine CBi-IGE model of trichinellosis, differing in susceptibility to this parasitosis (line CBi/L, resistant; line CBi+, susceptible). ABZ micro...
Source: AAPS PharmSciTech - May 20, 2020 Category: Drugs & Pharmacology Authors: Codina AV, Priotti J, Leonardi D, Vasconi MD, Hinrichsen LI, Lamas MC Tags: AAPS PharmSciTech Source Type: research

The Effect of Enzymes and Sodium Lauryl Sulfate on the Surface Tension of Dissolution Media: Toward Understanding the Solubility and Dissolution of Carvedilol.
The objective of this work was to study the effect of the physiologically relevant enzymes pepsin, pancreatin, and the synthetic surfactant sodium lauryl sulfate (SLS) on the surface tension of the dissolution media and the solubility and dissolution of the weakly basic drug carvedilol. Compendial dissolution media and buffer solutions that simulate the gastrointestinal fluid, prepared with and without the addition of SLS, were used in this study. The surface tension of the dissolution media; critical micelle concentration (CMC) of SLS in buffer solutions; and size, polydispersity index, and zeta potential of SLS micelles ...
Source: AAPS PharmSciTech - May 20, 2020 Category: Drugs & Pharmacology Authors: Hamed R, Alnadi SH, Awadallah A Tags: AAPS PharmSciTech Source Type: research

Robustness of Controlled Release Tablets Based on a Cross-linked Pregelatinized Potato Starch Matrix.
ert S Abstract The aim of this study was to evaluate the potential of a cross-linked pregelatinized potato starch (PREGEFLO® PI10) as matrix former for controlled release tablets. Different types of tablets loaded with diprophylline, diltiazem HCl or theophylline were prepared by direct compression of binary drug/polymer blends. The drug content was varied from 20 to 50%. Two hydroxypropyl methylcellulose grades (HPMC K100LV and K100M) were studied as alternative matrix formers. Drug release was measured in a variety of release media using different types of experimental set-ups. This includes 0.1 N HCl, ...
Source: AAPS PharmSciTech - May 20, 2020 Category: Drugs & Pharmacology Authors: Elgaied-Lamouchi D, Descamps N, Lefèvre P, Mackin-Mohamour AR, Neut C, Siepmann F, Siepmann J, Muschert S Tags: AAPS PharmSciTech Source Type: research

Correction to: Development of Nanocrystal Ziprasidone Orally Disintegrating Tablets: Optimization by Using Design of Experiment and In Vitro Evaluation.
Abstract Several typos occurred during the production process and captions were misplaced. The corrected captions for Picture 1, Fig. 6-9 are below. PMID: 32430673 [PubMed - in process] (Source: AAPS PharmSciTech)
Source: AAPS PharmSciTech - May 19, 2020 Category: Drugs & Pharmacology Authors: Tashan E, Karakucuk A, Celebi N Tags: AAPS PharmSciTech Source Type: research

Stimulatory Effects of Soluplus ® on Flufenamic Acid β-Cyclodextrin Supramolecular Complex: Physicochemical Characterization and Pre-clinical Anti-inflammatory Assessment.
Stimulatory Effects of Soluplus® on Flufenamic Acid β-Cyclodextrin Supramolecular Complex: Physicochemical Characterization and Pre-clinical Anti-inflammatory Assessment. AAPS PharmSciTech. 2020 May 19;21(5):145 Authors: Alshehri S, Imam SS, Altamimi MA, Hussain A, Shakeel F, Alshehri A Abstract The present study demonstrates the solubility and dissolution of flufenamic acid (FLF)/β-cyclodextrin (β-CD)/Soluplus® supramolecular ternary inclusion complex. The binary and ternary inclusion complexes were prepared using solvent evaporation and the microwave irradiation method. The pr...
Source: AAPS PharmSciTech - May 19, 2020 Category: Drugs & Pharmacology Authors: Alshehri S, Imam SS, Altamimi MA, Hussain A, Shakeel F, Alshehri A Tags: AAPS PharmSciTech Source Type: research

Spray-Dried Proliposomes: an Innovative Method for Encapsulation of Rosmarinus officinalis L. Polyphenols.
Abstract This work aims to improve the functionality of Rosmarinus officinalis L. (rosemary) polyphenols by encapsulation in an optimized proliposome formulation. A 23 Box-Wilson central composite design (CCD) was employed to determine lone and interaction effects of composition variables on moisture content (Xp); water activity (Aw); concentration and retention of rosemary polyphenols-rosmarinic acid (ROA), carnosol (CAR), and carnosic acid (CNA); and recovery of spray-dried proliposomes (SDP). Processing conditions which generate proliposomes with optimum physicochemical properties were determined by multi-respo...
Source: AAPS PharmSciTech - May 18, 2020 Category: Drugs & Pharmacology Authors: Bankole VO, Osungunna MO, Souza CRF, Salvador SL, Oliveira WP Tags: AAPS PharmSciTech Source Type: research

Formulation, Optimization and Evaluation of Novel Ultra-deformable Vesicular Drug Delivery System for an Anti-fungal Drug.
Abstract The present study is aimed at enhancing the skin penetration of ketoconazole by formulating it as transethosome. Ketoconazole-loaded transethosome formulations were prepared by conventional thin film evaporation and hydration method and were optimized using concentration of edge activator (span 80), ethanol and sonication time as factors and particle size, polydispersity index and entrapment efficiency as responses. The optimized formulation was further evaluated for in vitro diffusion, anti-fungal activity, ex vivo penetration and in vivo pharmacodynamic activity. The results of in vitro drug diffusion a...
Source: AAPS PharmSciTech - May 17, 2020 Category: Drugs & Pharmacology Authors: Nayak D, Tawale RM, Aranjani JM, Tippavajhala VK Tags: AAPS PharmSciTech Source Type: research

Chewable Antacid Tablets: Are Disintegration Tests Relevant?
This study evaluated disintegration as a quality attribute for a number of commercially available chewable antacid tablets. Additionally, acid-neutralizing-capacity values were evaluated. A number of the products exhibited prolonged disintegration times-which were far longer than those of conventional immediate-release tablets. The mean disintegration times ranged from 6 to more than 60 min in distilled water and from 9 to over 60 min in 0.1 N HCl. The products with longer disintegration times had higher breaking force and tensile strength values. Despite the range in disintegration times, all products met t...
Source: AAPS PharmSciTech - May 17, 2020 Category: Drugs & Pharmacology Authors: Nyamweya NN, Kimani SN, Abuga KO Tags: AAPS PharmSciTech Source Type: research

MUCO-DIS: a New AFM-Based Nanoscale Dissolution Technique.
Abstract Mucoadhesion-based drug delivery systems have recently gained interest because of their bio-adhesion capability, which results in enhanced residence time leading to prolonged duration of action with the mucosal surface, potentially improving compliance and convenience. Mucoadhesion testing of these formulations is widely reported; however, this is technically challenging due to the absence of any standard methods and difficulty in conducting mucoadhesion, formulation-mucosal surface interaction, mucosal surface topography and drug release in a single experiment. As these measurements are currently conduct...
Source: AAPS PharmSciTech - May 17, 2020 Category: Drugs & Pharmacology Authors: Ghori MU, Nirwan JS, Asim T, Chahid Y, Farhaj S, Khizer Z, Timmins P, Conway BR Tags: AAPS PharmSciTech Source Type: research

Self-Emulsifying Drug Delivery System of Celecoxib for Avoiding Delayed Oral Absorption in Rats with Impaired Gastric Motility.
This study aimed to develop a self-emulsifying drug delivery system (SEDDS) of celecoxib (CEL) for suppressed delay in oral absorption under impaired gastric motility. A pseudo-ternary phase diagram was constructed for the determination of the optimal component ratio in SEDDS of CEL (SEDDS/CEL), and the SEDDS/CEL was physicochemically characterized. A pharmacokinetic study on orally dosed CEL samples (5-mg CEL/kg) was carried out in normal and propantheline (PPT)-treated rats to mimic impaired gastric motility. SEDDS/CEL rapidly formed a fine emulsion with a mean size of 147 nm in distilled water and significantly imp...
Source: AAPS PharmSciTech - May 17, 2020 Category: Drugs & Pharmacology Authors: Yakushiji K, Sato H, Ogino M, Suzuki H, Seto Y, Onoue S Tags: AAPS PharmSciTech Source Type: research

Poloxamer-407-Co-Poly (2-Acrylamido-2-Methylpropane Sulfonic Acid) Cross-linked Nanogels for Solubility Enhancement of Olanzapine: Synthesis, Characterization, and Toxicity Evaluation.
In this study, nanogels, a promising system for solubility enhancement, were developed by free-radical polymerization technique. Different formulations were synthesized in which poloxamer-407 was cross-linked with 2-acrylamido-2-methylpropane sulfonic acid (AMPS) with the help of cross-linker methylene bisacrylamide (MBA). The chemically cross-linked nanogels were characterized by Fourier transform infrared spectroscopy (FT-IR), thermos gravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM), zeta size, swelling, sol-gel analysis, drug loading, solubi...
Source: AAPS PharmSciTech - May 17, 2020 Category: Drugs & Pharmacology Authors: Khan KU, Akhtar N, Minhas MU Tags: AAPS PharmSciTech Source Type: research

The Application of Coarse-Grained Molecular Dynamics to the Evaluation of Liposome Physical Stability.
In this study, to speed up the research efficiency, coarse-grained molecular dynamics was first applied in the study of liposome physical stability. By analyzing the microprocess of vesicle fusion, two parameters including diffusion constant and the total time of the vesicle morphology transition process were employed to study the liposome physical stability. Then, in order to verify the applicability of two parameters, the physical stability of elastic liposomes and conventional liposomes was compared at 3 different temperatures. It was found that the fusion probability and speed of elastic liposomes were higher than thos...
Source: AAPS PharmSciTech - May 17, 2020 Category: Drugs & Pharmacology Authors: Chen L, Wu Z, Wu X, Liao Y, Dai X, Shi X Tags: AAPS PharmSciTech Source Type: research

An NMR Protocol for In Vitro Paclitaxel Release from an Albumin-Bound Nanoparticle Formulation.
Abstract The paclitaxel protein-bound particles for injectable suspension (marketed under the brand name Abraxane®) contains nanosized complexes of paclitaxel and albumin. The molecular interaction between paclitaxel and albumin within the higher-order nanostructure is analytically challenging to assess, as is any correlation of differences to differences in therapeutic effect. However, because the higher-order nanostructures may affect the paclitaxel release, a suitable in vitro assay to detect potential differences in paclitaxel release between comparator lots and products is desirable. Herein, solution NMR ...
Source: AAPS PharmSciTech - May 17, 2020 Category: Drugs & Pharmacology Authors: Suh MS, Patil SM, Kozak D, Pang E, Choi S, Jiang X, Rodriguez JD, Keire DA, Chen K Tags: AAPS PharmSciTech Source Type: research

Optimization of Thymoquinone-Loaded Coconut Oil Nanostructured Lipid Carriers for the Management of Ethanol-Induced Ulcer.
Abstract In the global incidence of peptic ulcer, with the associated rates of hospitalizations and mortality are increasing, in the United States, peptic ulcer disease affects approximately 4.6 million people annually, with an estimated 10% of the US population having evidence of a duodenal ulcer. The present research aims to find a novel treatment for ethanol induced ulcer by loading thymoquinone (TQ) on a nanostructured lipid carrier (NLC), using Compritol® 888 and coconut oil. The TQ-loaded coconut oil NLC was formulated using melt emulsification combined with a sonication method using Poloxamer 188 as a s...
Source: AAPS PharmSciTech - May 17, 2020 Category: Drugs & Pharmacology Authors: Fahmy UA, L Alaofi A, Awan ZA, Alqarni HM, Alhakamy NA Tags: AAPS PharmSciTech Source Type: research

Cationic Polylactic Acid-Based Nanoparticles Improve BSA-FITC Transport Across M Cells and Engulfment by Porcine Alveolar Macrophages.
Abstract This work described the development of a cationic polylactic acid (PLA)-based nanoparticles (NPs) as an antigen delivery system using dimethyldioctadecylammonium bromide (DDA) to facilitate the engulfment of BSA-FITC by porcine alveolar macrophages (3D4/2 cells) and heat-labile enterotoxin subunit B (LTB) to enhance the transport of BSA-FITC across M cells. The experimental design methodology was employed to study the influence of PLA, polyvinyl alcohol (PVA), DDA, and LTB on the physical properties of the PLA-based NPs. The size of selected cationic PLA NPs comprising 5% PLA, 5% PVA, and 0.6% DDA with or...
Source: AAPS PharmSciTech - May 15, 2020 Category: Drugs & Pharmacology Authors: Chaikhumwang P, Kitsongsermthon J, Manopakdee K, Chongcharoen W, Nilubol D, Chanvorachote P, Somparn P, Tantituvanont A Tags: AAPS PharmSciTech Source Type: research

The Stabilizing Excipients in Dry State Therapeutic Phage Formulations.
Abstract Phage therapy has gained prominence due to the increasing pathogenicity of "super bugs" and the rise of their multidrug resistance to conventional antibiotics. Dry state formulation of therapeutic phage is attractive to improve their "druggability" by increasing their shelf life, improving their ease of handling, and ultimately retaining their long-term potency. The use and selection of excipients are critical to stabilize phage in solid formulations and protect their viability from stresses encountered during the solidification process and long-term storage prior to use. Here, this re...
Source: AAPS PharmSciTech - May 15, 2020 Category: Drugs & Pharmacology Authors: Zhang Y, Zhang H, Ghosh D Tags: AAPS PharmSciTech Source Type: research

Factors Influencing the Delivery Efficiency of Cancer Nanomedicines.
Abstract The superiority of nanomedicine over conventional medicines in the treatment of cancer has gained immediate recognition worldwide. As traditional cancer therapies are nonspecific and detrimental to healthy cells, the ability of nanomedicine to release drugs to target tumor cells specifically instead of healthy cells has brought new hope to cancer patients. This review focuses on the effects of various factors of nanoparticles such as transport, concentration in cells, tumor microenvironment, interaction with protein, penetration, uptake by tumor cells, cancer cell mutations, and intracellular trafficking ...
Source: AAPS PharmSciTech - May 14, 2020 Category: Drugs & Pharmacology Authors: Ullah R, Wazir J, Khan FU, Diallo MT, Ihsan AU, Mikrani R, Aquib M, Zhou X Tags: AAPS PharmSciTech Source Type: research

Research Progress of Drug Treatment in Novel Coronavirus Pneumonia.
Abstract As of March 10, 2020, more than 100,000 novel coronavirus pneumonia cases have been confirmed globally. With the continuous spread of the new coronavirus pneumonia epidemic in even the world, prevention and treatment of the disease have become urgent tasks. The drugs currently being developed are not adequate to deal with this critical situation. In addition to being controlled through effective isolation, we need a rapid response from the healthcare and biotechnology industries to accelerate drug treatment research. By reviewing the currently available literature published at home and abroad, we summariz...
Source: AAPS PharmSciTech - May 13, 2020 Category: Drugs & Pharmacology Authors: Yan J, Liu A, Huang J, Wu J, Fan H Tags: AAPS PharmSciTech Source Type: research

In Vitro Release of 5-Fluorouracil and Methotrexate from Different Thermosensitive Chitosan Hydrogel Systems.
Abstract 5-Fluorouracil is a member of cytotoxic drugs with poor selectivity to cancer cells. Currently, systemic administration of this anti-cancer drug (oral or injection) exposes normal tissues to the drug-induced toxicity. Nowadays, attention has been greatly directed towards in situ gel-forming systems that can be injected into the affected tissues in its sol form with a minimally invasive technique. More specifically, chitosan hydrogel systems were in focus due to their antibacterial effect as well as their biodegradable, biocompatible, and mucoadhesive properties. In the present work, 5-fluorouracil was loa...
Source: AAPS PharmSciTech - May 13, 2020 Category: Drugs & Pharmacology Authors: Mohammed AM, Osman SK, Saleh KI, Samy AM Tags: AAPS PharmSciTech Source Type: research

Characterization, Optimization, In Vitro and In Vivo Evaluation of Simvastatin Proliposomes, as a Drug Delivery.
Abstract Simvastatin a cholesterol-lowering agent used to treat hypercholesterolemia, coronary heart disease, and dyslipidemia. However, simvastatin (SV) has shown low oral bioavailability in GIT. The main purpose of the work was to develop proliposomal formulations to increase the oral bioavailability of SV. Film deposition on the carrier method has been used to prepare the proliposomes. The proliposomes were assessed for morphology, particulate size, entrapment efficacy, drug-polymer compatibility, in vitro and in vivo studies. FTIR and DSC results revealed no drug-polymer interaction. SEM and XRD analysis confo...
Source: AAPS PharmSciTech - May 13, 2020 Category: Drugs & Pharmacology Authors: Rahamathulla M, H V G, Veerapu G, Hani U, Alhamhoom Y, Alqahtani A, Moin A Tags: AAPS PharmSciTech Source Type: research

Evaluation of the Physico-mechanical Properties and Electrostatic Charging Behavior of Different Capsule Types for Inhalation Under Distinct Environmental Conditions.
Abstract Capsule-based dry powder inhaler (DPI) products can be influenced by a multitude of interacting factors, including electrostatic charging. Tribo-charging is a process of charge transfer impacted by various factors, i.e., material surface characteristics, mechanical properties, processing parameters and environmental conditions. Consequently, this work aimed to assess how the charging behavior of capsules intended for inhalation might be influenced by environmental conditions. Capsules having different chemical compositions (gelatin and hydroxypropyl methylcellulose (HPMC)) and distinct inherent characteri...
Source: AAPS PharmSciTech - May 12, 2020 Category: Drugs & Pharmacology Authors: Pinto JT, Wutscher T, Stankovic-Brandl M, Zellnitz S, Biserni S, Mercandelli A, Kobler M, Buttini F, Andrade L, Daza V, Ecenarro S, Canalejas L, Paudel A Tags: AAPS PharmSciTech Source Type: research

Quality Risk Management and Quality by Design for the Development of Diclofenac Sodium Intra-articular Gelatin Microspheres.
Abstract The aim of the present study was to evaluate the development of an intra-articular nonsteroidal anti-inflammatory drug gelatin microsphere formulation based on quality risk management and quality by design approaches. Specifically, after setting the quality target product profile and the critical quality attributes, risk assessment was performed by constructing Ishikawa fishbone diagrams based on preliminary hazard analysis. A Plackett-Burman screening experimental design was applied in order to identify the factors (previously classified by risk assessment analysis as having high risk of failure) having ...
Source: AAPS PharmSciTech - May 10, 2020 Category: Drugs & Pharmacology Authors: Nakas A, Dalatsi AM, Kapourani A, Kontogiannopoulos KN, Assimopoulou AN, Barmpalexis P Tags: AAPS PharmSciTech Source Type: research

A Novel Technique to Improve Drug Loading Capacity of Fast/Extended Release Orally Dissolving Films with Potential for Paediatric and Geriatric Drug Delivery.
This study provides a mechanistic insight to the design and evaluation of fast and extended release ODFs with high drug loading, suitable for administration to paediatric and geriatric patients. PMID: 32382992 [PubMed - in process] (Source: AAPS PharmSciTech)
Source: AAPS PharmSciTech - May 7, 2020 Category: Drugs & Pharmacology Authors: Ouda GI, Dahmash EZ, Alyami H, Iyire A Tags: AAPS PharmSciTech Source Type: research

Synthesis and Characterization of Nanostructured Lipid Nanocarriers for Enhanced Sun Protection Factor of Octyl p-methoxycinnamate.
This study aimed at producing a stable octyl p-methoxycinnamate (OMC)-loaded nanostructured lipid carrier (NLC) sunscreen, which can help in the photoprotective effect. NLC was produced by emulsification-sonication method and these systems were composed of myristyl myristate (MM), caprylic capric triglyceride (CCT), Tween® 80 (TW), and soybean phosphatidylcholine (SP) and characterized by dynamic light scattering (DLS), zeta potential (ZP) measurement, atomic force microscopy (AFM), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and in vitro release studies. Pre-formulation studies were pe...
Source: AAPS PharmSciTech - April 29, 2020 Category: Drugs & Pharmacology Authors: do Prado AH, Araújo VHS, Eloy JO, Fonseca-Santos B, Pereira-da-Silva MA, Peccinini RG, Chorilli M Tags: AAPS PharmSciTech Source Type: research

SP94 Peptide-Functionalized PEG-PLGA Nanoparticle Loading with Cryptotanshinone for Targeting Therapy of Hepatocellular Carcinoma.
Abstract To achieve improved drug delivery efficiency to hepatocellular carcinoma (HCC), biodegradable poly (ethylene glycol)-poly (lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (NP), surface-modified with SP94 peptide, were designed for the efficient delivery of cryptotanshinone to the tumor for the treatment of HCC. Cryptotanshinone NP and SP94-NP were prepared by using nanoprecipitation. The physicochemical and pharmaceutical properties of the NP and SP94-NP were characterized, and the release kinetics suggested that both NP and SP94-NP provided continuous, slow release of cryptotanshinone for 48 h. Th...
Source: AAPS PharmSciTech - April 27, 2020 Category: Drugs & Pharmacology Authors: Nie X, Liu Y, Li M, Yu X, Yuan W, Huang S, Ren D, Wang Y, Wang Y Tags: AAPS PharmSciTech Source Type: research

The Role of Surface Properties on Protein Aggregation Behavior in Aqueous Solution of Different pH Values.
This study aimed to investigate the effect of pH-mediated surface properties of bovine serum albumin (BSA) on protein aggregation and the changes of protein structure and colloidal stability at different solution pH levels. The hydrophobicity of BSA surface was characterized by endogenous fluorescence spectroscopy, fluorescence quenching of acrylamide, and fluorescence probe. The results showed that the hydrophobicity of BSA surface was similar at pH 5, 6, 7.4, followed by pH 4, 8, 9, 10, and finally by pH 3 and 11 with strong acidity and alkalinity. The positive charge on the BSA surface was increased gradu...
Source: AAPS PharmSciTech - April 26, 2020 Category: Drugs & Pharmacology Authors: Lan H, Liu H, Ye Y, Yin Z Tags: AAPS PharmSciTech Source Type: research

Chemotherapeutic Efficacy Enhancement in P-gp-Overexpressing Cancer Cells by Flavonoid-Loaded Polymeric Micelles.
In this study, the polymeric micelles of benzoylated methoxy-poly (ethylene glycol)-b-oligo(ε-caprolactone) or mPEG-b-OCL-Bz loading with the flavonoids were prepared to solve these problems. The flavonoid-loaded micelles showed an average size of 13-20 nm and maximum loading capacity of 35% (w/w). The release of QCT (21%, 3 h) was lower than that of QTR (51%, 3 h) and RUT (58%, 3 h). QCT (free and micelle forms) exhibited significantly higher cytotoxicity against P-glycoprotein-overexpressing leukemia (K562/ADR) cells than QTR and RUT (p 
Source: AAPS PharmSciTech - April 26, 2020 Category: Drugs & Pharmacology Authors: Khonkarn R, Daowtak K, Okonogi S Tags: AAPS PharmSciTech Source Type: research

Evaluation of Mogroside V as a Promising Carrier in Drug Delivery: Improving the Bioavailability and Liver Distribution of Silybin.
The objective of this work was to investigate the capacity of mogroside V (MOG-V), a food additive, as a novel carrier to improve the bioavailability and liver distribution of silybin (SLY). Solid dispersion particles (SDPs) of SLY/MOG-V were prepared utilizing the solvent evaporation method. The physicochemical characterizations of SDPs were evaluated by using dynamic light scattering (DLS), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD) measurements. DLS results demonstrated the formation of nanoparticles (206 nm) of SDPs in water. DSC and PXRD analysis revealed that SLY was in amorphou...
Source: AAPS PharmSciTech - April 26, 2020 Category: Drugs & Pharmacology Authors: Luo Y, Gong C, Wei M, Chen Y, Song T, Wu C, Mo L, Zhang J Tags: AAPS PharmSciTech Source Type: research

Cold Flow Evaluation in Transdermal Drug Delivery Systems by Measuring the Width of the Oozed Adhesive.
The objective of this study was to develop a simpler and more practical quantitative evaluation method of cold flow (CF) in transdermal drug delivery systems (TDDSs). CF was forcibly induced by loading a weight on a punched-out sample (bisoprolol and tulobuterol tapes). When the extent of CF was analyzed using the area of oozed adhesive as following a previously reported method, the CF profiles were looked different between the samples 12 mm in diameter subjected to a 0.5-kg weight and samples 24 mm in diameter subjected to a 2.0-kg weight despite an equal load per unit area (4.42 g/mm2). The width of oozed ...
Source: AAPS PharmSciTech - April 22, 2020 Category: Drugs & Pharmacology Authors: Miyazaki T, Kanno H, Yamamoto E, Ando D, Izutsu KI, Goda Y Tags: AAPS PharmSciTech Source Type: research

Improved Oral Pharmacokinetics of Pentoxifylline with Palm Oil and Capmul ® MCM Containing Self-Nano-Emulsifying Drug Delivery System.
In conclusion, SNEDDS was seen to enhance the bioavailability of PTX and can be explored to effectively control the incidents of intermittent claudication. PMID: 32318890 [PubMed - in process] (Source: AAPS PharmSciTech)
Source: AAPS PharmSciTech - April 21, 2020 Category: Drugs & Pharmacology Authors: Shailendrakumar AM, Ghate VM, Kinra M, Lewis SA Tags: AAPS PharmSciTech Source Type: research

Preparation, Physicochemical Characterisation and DoE Optimisation of a Spray-Dried Dry Emulsion Platform for Delivery of a Poorly Soluble Drug, Simvastatin.
Abstract In the presented study, insight into the development and optimisation of the dry emulsion formulation and spray drying process is provided. The aim was to facilitate the dissolution of the poorly soluble, highly lipophilic drug, simvastatin, by forming spray-dried dry emulsion particles having adequate powder flow properties, while assuring sufficient drug content. Simvastatin and a mixture of caprylic, capric triglyceride and 1-oleoyl-rac-glycerol were employed as a model drug and solubilising oils, respectively. A matrix of the dry emulsions was composed at a fixed ratio mixture of mannitol and HPMC. Tw...
Source: AAPS PharmSciTech - April 21, 2020 Category: Drugs & Pharmacology Authors: Pohlen M, Lavrič Z, Prestidge C, Dreu R Tags: AAPS PharmSciTech Source Type: research

Determination of Rate and Extent of Scopolamine Release from Transderm Sc ōp® Transdermal Drug Delivery Systems in Healthy Human Adults.
Determination of Rate and Extent of Scopolamine Release from Transderm Scōp® Transdermal Drug Delivery Systems in Healthy Human Adults. AAPS PharmSciTech. 2020 Apr 16;21(3):117 Authors: Swaminathan SK, Strasinger C, Kelchen M, Carr J, Ye W, Wokovich A, Ghosh P, Rajagopal S, Ueda K, Fisher J, Kandimalla KK, Brogden NK Abstract To estimate strength of a scopolamine transdermal delivery system (TDS) in vivo, using residual drug vs. pharmacokinetic analyses with the goal of scientifically supporting a single and robust method for use across the dosage form and ultimately facilitate the development of...
Source: AAPS PharmSciTech - April 16, 2020 Category: Drugs & Pharmacology Authors: Swaminathan SK, Strasinger C, Kelchen M, Carr J, Ye W, Wokovich A, Ghosh P, Rajagopal S, Ueda K, Fisher J, Kandimalla KK, Brogden NK Tags: AAPS PharmSciTech Source Type: research

Quantification of Monomer Units in Insoluble Polymeric Active Pharmaceutical Ingredients Using Solid-State NMR Spectroscopy I: Patiromer.
Abstract Although extensive precautions are taken to limit batch-to-batch variation in pharmaceutical manufacturing, differences between lots may still exist, particularly in complex formulations. When polymerization is used in the production process, the potential for varying chain lengths and incorporation of different monomers increases the likelihood of batch-to-batch variation. This poses a significant challenge for demonstrating active pharmaceutical ingredient (API) sameness between the innovator and generic drug under development. Therefore, the ability to accurately analyze and quantify the relative amoun...
Source: AAPS PharmSciTech - April 15, 2020 Category: Drugs & Pharmacology Authors: Jarrells TW, Zhang D, Li S, Munson EJ Tags: AAPS PharmSciTech Source Type: research

The Route to Palatable Fecal Microbiota Transplantation.
Abstract The community of symbiotic microorganisms that reside in our gastrointestinal tract is integral to human health. Fecal microbiota transplantation (FMT) has been shown to be highly effective in treating recurrent Clostridioides difficile infection (rCDI) and is now recommended by medical societies for patients suffering from rCDI who have failed to respond to conventional therapy. The main challenges with FMT are its accessibility, acceptability, lack of standardization, and regulatory complexity, which will be discussed in this review. Access to FMT is being addressed through the development of frozen and...
Source: AAPS PharmSciTech - April 15, 2020 Category: Drugs & Pharmacology Authors: Fadda HM Tags: AAPS PharmSciTech Source Type: research

Development of Nanocrystal Ziprasidone Orally Disintegrating Tablets: Optimization by Using Design of Experiment and In Vitro Evaluation.
In conclusion, the novel formulation of ZHM nanocrystal-based ODTs was successfully developed for alternative dosage form. PMID: 32296987 [PubMed - in process] (Source: AAPS PharmSciTech)
Source: AAPS PharmSciTech - April 15, 2020 Category: Drugs & Pharmacology Authors: Tashan E, Karakucuk A, Celebi N Tags: AAPS PharmSciTech Source Type: research

Novel Enhanced Therapeutic Efficacy of Dapoxetine HCl by Nano-Vesicle Transdermal Gel for Treatment of Carrageenan-Induced Rat Paw Edema.
In conclusion, developed NVTG formulation loaded with dapoxetine HCl (DH) offers new opportunities for creating novel therapeutic modality for inflammation patients with fewer adverse effects. PMID: 32291553 [PubMed - in process] (Source: AAPS PharmSciTech)
Source: AAPS PharmSciTech - April 14, 2020 Category: Drugs & Pharmacology Authors: Salem HF, Nafady MM, Kharshoum RM, Abd El-Ghafar OA, Farouk HO Tags: AAPS PharmSciTech Source Type: research

Data-Driven Modeling of the Bicalutamide Dissolution from Powder Systems.
icz R Abstract Low solubility of active pharmaceutical compounds (APIs) remains an important challenge in dosage form development process. In the manuscript, empirical models were developed and analyzed in order to predict dissolution of bicalutamide (BCL) from solid dispersion with various carriers. BCL was chosen as an example of a poor water-soluble API. Two separate datasets were created: one from literature data and another based on in-house experimental data. Computational experiments were conducted using artificial intelligence tools based on machine learning (AI/ML) with a plethora of techniques including ...
Source: AAPS PharmSciTech - March 31, 2020 Category: Drugs & Pharmacology Authors: Mendyk A, Pacławski A, Szafraniec-Szczęsny J, Antosik A, Jamróz W, Paluch M, Jachowicz R Tags: AAPS PharmSciTech Source Type: research

A Novel Prototype Device for Microencapsulation of Benznidazole: In Vitro/In Vivo Studies.
This study was aimed to design a simple and novel prototype device for the production of polymeric microparticles. To prove the effectiveness of this device, benznidazole microparticles using chitosan as carrier and NaOH, KOH, or SLS as counter ions were used. For comparison, benznidazole microparticles were prepared by the conventional dripping technique (syringe and gauge) using the same excipients. Microparticles were characterized in terms of encapsulation efficiency, particle shape, size and surface topography, crystallinity characteristics, thermal behavior, and dissolution rate. Then, the pharmacokinetic parameters ...
Source: AAPS PharmSciTech - March 31, 2020 Category: Drugs & Pharmacology Authors: Barrera MG, Tejada G, Leonardi D, Lamas MC, Salomón CJ Tags: AAPS PharmSciTech Source Type: research

Combined Therapy for Alzheimer's Disease: Tacrine and PAMAM Dendrimers Co-Administration Reduces the Side Effects of the Drug without Modifying its Activity.
In conclusion, the co-administration of TAC with both DG4.0 and DG4.5 is a novel therapy since it was less-toxic, was more biocompatible, and has the same effectiveness than the free drug. Graphical abstract. PMID: 32215751 [PubMed - in process] (Source: AAPS PharmSciTech)
Source: AAPS PharmSciTech - March 25, 2020 Category: Drugs & Pharmacology Authors: Igartúa DE, Martinez CS, Del V Alonso S, Prieto MJ Tags: AAPS PharmSciTech Source Type: research

Lyophilisation Improves Bioactivity and Stability of Insulin-Loaded Polymeric-Oligonucleotide Nanoparticles for Diabetes Treatment.
In this study, nanoparticles were fabricated by cationic chitosan and anionic Dz13Scr using complex coacervation. The effect of cryoprotectant types (mannitol, sorbitol, sucrose and trehalose) and their concentrations (1, 3, 5, 7, 10% w/v) on physiochemical properties of nanoparticles were measured. Cellular assays were performed to investigate the impact of selected cryoprotectant on cytotoxicity, glucose consumption, oral absorption mechanism and gastrointestinal permeability. The obtained results revealed that mannitol (7% w/v) could produce nanoparticles with small size (313.2 nm), slight positive charge and unifo...
Source: AAPS PharmSciTech - March 25, 2020 Category: Drugs & Pharmacology Authors: Wong CY, Al-Salami H, Dass CR Tags: AAPS PharmSciTech Source Type: research

Transdermal Delivery of the Free Base of 3-Fluoroamphetamine: In Vitro Skin Permeation and Irritation Potential.
In conclusion, the present study further supported the development of PAL-353 transdermal delivery systems. PMID: 32215773 [PubMed - in process] (Source: AAPS PharmSciTech)
Source: AAPS PharmSciTech - March 25, 2020 Category: Drugs & Pharmacology Authors: Jiang Y, Murnane KS, Blough BE, Banga AK Tags: AAPS PharmSciTech Source Type: research

Effects of Uncleavable and Cleavable PEG-Lipids with Different Molecular Weights on Accelerated Blood Clearance of PEGylated Emulsions in Beagle Dogs.
Abstract To investigate the effect of polyethylene glycol (PEG) molecular weights on circulation time of PEGylated emulsions and the second injection of injected PEGylated emulsions, we studied the effect of molecular weights on the pharmacokinetic behavior of PEG-DSPE (modified emulsions with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-n-[methoxy (polyethyleneglycol)]) and PEG-CHMC (modified emulsions with poly(ethyleneglycol)-cholesteryl carbonate) emulsions in beagle dogs. The "accelerated blood clearance" (ABC) phenomenon was induced. Through this study, the contribution of PEG molecular weights ...
Source: AAPS PharmSciTech - March 17, 2020 Category: Drugs & Pharmacology Authors: Jiao J, Luo X, Wang C, Jiao X, Liu M, Liu X, Wei L, Deng Y, Song Y Tags: AAPS PharmSciTech Source Type: research