Eco-Friendly Tadalafil Surfactant-Free Dry Emulsion Tablets (SFDETs) Stabilized by In Situ Self-Assembled Aggregates of Natural Oil and Native Cyclodextrins.
Abstract The main principles of green chemistry and engineering were extended to pharmaceutical formulations to prepare eco-friendly surfactant-free dry emulsion tablets (SFDETs) devoid of solvents or synthetic surfactants. Surfactant-free emulsions were stabilized by in situ cyclodextrins/sweet almond oil inclusion complexes and assessed for creaming stability. Formulation variables' effects on the emulsion droplet size and tadalafil solubility were studied using 22 × 3 factorial design. The emulsions exhibited nanometric and micrometric droplet sizes. The optimized nanoemulsion was loaded wit...
Source: AAPS PharmSciTech - July 18, 2019 Category: Drugs & Pharmacology Authors: Badr-Eldin SM, Labib GS, Aburahma MH Tags: AAPS PharmSciTech Source Type: research

Self-Assembling Topical Nanomicellar Formulation to Improve Curcumin Absorption Across Ocular Tissues.
Abstract The pathophysiological mechanisms for dry and wet age-related macular degeneration (AMD) involve oxidative stress and increased VEGF release and expression. An ideal drug candidate for both types of AMD is the one which offers significant protection to the retinal cells from oxidative stress and inhibit VEGF release. Curcumin is one such natural product which provides numerous beneficial effects including antioxidant, anti-inflammatory, and anti-VEGF activities and has the potential for the treatment of both types of AMD. The bioavailability of curcumin is negligible due to its poor aqueous solubility. Th...
Source: AAPS PharmSciTech - July 17, 2019 Category: Drugs & Pharmacology Authors: Alshamrani M, Sikder S, Coulibaly F, Mandal A, Pal D, Mitra AK Tags: AAPS PharmSciTech Source Type: research

Chitosan-Based Drug Delivery Systems for Optimization of Photodynamic Therapy: a Review.
Abstract Drug delivery systems (DDS) can be designed to enrich the pharmacological and therapeutic properties of several drugs. Many of the initial obstacles that impeded the clinical applications of conventional DDS have been overcome with nanotechnology-based DDS, especially those formed by chitosan (CS). CS is a linear polysaccharide obtained by the deacetylation of chitin, which has potential properties such as biocompatibility, hydrophilicity, biodegradability, non-toxicity, high bioavailability, simplicity of modification, aqueous solubility, and excellent chemical resistance. Furthermore, CS can prepare sev...
Source: AAPS PharmSciTech - July 15, 2019 Category: Drugs & Pharmacology Authors: Calixto GMF, de Annunzio SR, Victorelli FD, Frade ML, Ferreira PS, Chorilli M, Fontana CR Tags: AAPS PharmSciTech Source Type: research

Quality-by-Design Approach for Biological API Encapsulation into Polymersomes Using "Off-the-Shelf" Materials: a Study on L-Asparaginase.
Quality-by-Design Approach for Biological API Encapsulation into Polymersomes Using "Off-the-Shelf" Materials: a Study on L-Asparaginase. AAPS PharmSciTech. 2019 Jul 12;20(6):251 Authors: Apolinário AC, Ferraro RB, de Oliveira CA, Pessoa A, de Oliveira Rangel-Yagui C Abstract Polymersomes are versatile nanostructures for protein delivery with hydrophilic core suitable for large biomolecule encapsulation and protective stable corona. Nonetheless, pharmaceutical products based on polymersomes are not available in the market, yet. Here, using commercially available copolymers, we investi...
Source: AAPS PharmSciTech - July 12, 2019 Category: Drugs & Pharmacology Authors: Apolinário AC, Ferraro RB, de Oliveira CA, Pessoa A, de Oliveira Rangel-Yagui C Tags: AAPS PharmSciTech Source Type: research

Curcumin-Loaded Nanostructured Lipid Carrier Modified with Partially Hydrolyzed Ginsenoside.
The objective of the present study was to investigate the effect of partially hydrolyzed ginsenoside on the physicochemical properties and in vitro release of curcumin from phospholipid-based nanostructured lipid carrier (NLC). NLC formulas modified with partially hydrolyzed ginsenoside (NLC-PG) were prepared with different amounts of ginsenoside using the conventional hot-melt method. The average particle size of curcumin-loaded NLC-PG ranged from 150 to 200 nm, and polydispersity index was in the range of 0.101-0.177, indicating monodispersed particle size distribution. Optical microscopy showed no sedimentation or ...
Source: AAPS PharmSciTech - July 12, 2019 Category: Drugs & Pharmacology Authors: Selvaraj K, Yoo BK Tags: AAPS PharmSciTech Source Type: research

Pharmaceutical Topical Delivery of Poorly Soluble Polyphenols: Potential Role in Prevention and Treatment of Melanoma.
Abstract Melanoma is regarded as the fifth and sixth most common cancer in men and women, respectively, and it is estimated that one person dies from melanoma every hour in the USA. Unfortunately, the treatment of melanoma is difficult because of its aggressive metastasis and resistance to treatment. The treatment of melanoma continues to be a challenging issue due to the limitations of available treatments such as a low response rate, severe adverse reactions, and significant toxicity. Natural polyphenols have attracted considerable attention from the scientific community due to their chemopreventive and chemothe...
Source: AAPS PharmSciTech - July 11, 2019 Category: Drugs & Pharmacology Authors: Heenatigala Palliyage G, Singh S, Ashby CR, Tiwari AK, Chauhan H Tags: AAPS PharmSciTech Source Type: research

Highly Water-Soluble Methotrexate-Polyethyleneglycol-Rhodamine Prodrug Micelle for High Tumor Inhibition Activity.
Abstract Highly water-soluble prodrug micelle (50-fold compared with free MTX) of methotrexate-polyethyleneglycol-rhodamine (MTX-PEG-rhodamine) and MTX-mPEG was synthesized by the esterification reaction. The stability of the prodrug micelles was evaluated in phosphate buffer saline (PBS) with 10% fetal bovine serum (FBS). The tumor volume of the saline, MTX, and MTX-PEG-rhodamine groups was increased 3.7-fold, 2.8-fold, and 1.8-fold, respectively, compared with the initial tumor volume. TUNEL and drug distribution results further confirmed that the micelle of MTX-PEG-rhodamine possessed fewer side effects on the ...
Source: AAPS PharmSciTech - July 8, 2019 Category: Drugs & Pharmacology Authors: Duan X, Yang X, Li C, Song L Tags: AAPS PharmSciTech Source Type: research

Effects of β-Cyclodextrin and Hydroxypropyl-β-Cyclodextrin Inclusions on the Degradation of Magnolol by Intestinal Bacteria.
In conclusion, the inclusion complexes partially protected MAG from degradation by the intestinal bacteria. PMID: 31286296 [PubMed - in process] (Source: AAPS PharmSciTech)
Source: AAPS PharmSciTech - July 8, 2019 Category: Drugs & Pharmacology Authors: Tang L, Zhu Z, Xie M, Cao L, Yu XL, Zhang R, Ou Z, Shan W, Zhang Z Tags: AAPS PharmSciTech Source Type: research

Dentifrice Based on Fluoride-Hydrotalcite Compounds: Characterization and Release Capacity Evaluation by Novel In Vitro Methods.
Abstract Anti-caries activity of fluoride ions is due to the protection against demineralization and the enhancement of remineralization of tooth enamel. Dentifrices available on the market contain sodium fluoride, sodium monofluorophosphate, stannous fluoride, and amine fluoride as source of these ions. A new compound working both as fluoride ion source and as abrasive was projected. Hybrids based on F- ions intercalated between the lamellae of hydrotalcite-like compounds (HTlc-F), namely MgAl-HTlc-F and ZnAl-HTlc-F, were prepared and characterized. Then, three different percentages (2, 3, and 4%) of both HTlc-F ...
Source: AAPS PharmSciTech - July 8, 2019 Category: Drugs & Pharmacology Authors: Pagano C, Perioli L, Marmottini F, Ramella D, Tiralti MC, Ricci M Tags: AAPS PharmSciTech Source Type: research

Development and Qualification of a Scale-Down Mammalian Cell Culture Model and Application in Design Space Development by Definitive Screening Design.
In this study, a scale-down model representing commercial-scale cell culture process of adalimumab biosimilar HS016 was first developed based on constant power per volume (P/V) principle and then qualified by multivariate data analysis (MVDA) and equivalence test method. The trajectories of the bench-scale process lie in the middle of the control range of large-scale process, built by multivariate evolution model based on nutrients, metabolites, and process performance datasets. This indicates that the small-scale process performance is comparable with that of the full-scale process. The final product titer, integrated via...
Source: AAPS PharmSciTech - July 8, 2019 Category: Drugs & Pharmacology Authors: Nie L, Gao D, Jiang H, Gou J, Li L, Hu F, Guo T, Wang H, Qu H Tags: AAPS PharmSciTech Source Type: research

Cascade Impactor Equivalence Testing: Comparison of the Performance of the Modified Chi-Square Ratio Statistic (mCSRS) with the Original CSRS and EMA's Average Bioequivalence Approach.
Abstract The performances of three statistical approaches for assessing in vitro equivalence was evaluated with a set of 55 scenarios of realistic test (T) and reference (R) cascade impactor (CI) profiles (originally employed by the Product Quality Research Institute to evaluate the chi-square ratio statistic: CSRS) by comparing the outcomes against experts' opinion (surrogate for the truth). The three methods were (A) a stepwise aerodynamic particle size distribution (APSD) equivalence test integrating population bioequivalence (PBE) testing of impactor-sized mass (ISM) with the CSRS (PBE-CSRS approach), previous...
Source: AAPS PharmSciTech - July 8, 2019 Category: Drugs & Pharmacology Authors: Kurumaddali A, Christopher D, Sandell D, Strickland H, Morgan B, Bulitta J, Wiggenhorn C, Stein S, Lyapustina S, Hochhaus G Tags: AAPS PharmSciTech Source Type: research

The Pharmacokinetic Prediction of Cyclosporin A after Coadministration with Wuzhi Capsule.
Abstract We aim to describe the influence of principal ingredients of Wuzhi capsule, schisandrin A (SIA) and schisantherin A (STA), on the pharmacokinetics of cyclosporin A (CsA) and to quantify the herb-drug interactions (HDIs) between SIA, STA, and CsA. CsA is a first-line immunosuppressant for anti-rejection therapy after solid organ transplantation, while narrow therapeutic window associated with strong hepatotoxicity largely limited its use. Wuzhi capsule, a liver-protective drug, was approved for coadministration with CsA to reduce the hepatotoxicity. There are few studies exploring HDIs of CsA when coadmini...
Source: AAPS PharmSciTech - July 8, 2019 Category: Drugs & Pharmacology Authors: Fan J, Chen L, Lu X, Li M, Zhu L Tags: AAPS PharmSciTech Source Type: research

In silico Tools at Early Stage of Pharmaceutical Development: Data Needs and Software Capabilities.
g R Abstract In early drug development, the selection of a formulation platform and decisions on formulation strategies have to be made within a short timeframe and often with minimal use of the active pharmaceutical ingredient (API). The current work evaluated the various physicochemical parameters required to improve the prediction accuracy of simulation software for immediate release tablets in early drug development. DDDPlus™ was used in simulating dissolution test profiles of immediate release tablets of ritonavir and all simulations were compared with experimental results. The minimum data requirements...
Source: AAPS PharmSciTech - July 1, 2019 Category: Drugs & Pharmacology Authors: Njoku JO, Amaral Silva D, Mukherjee D, Webster GK, Löbenberg R Tags: AAPS PharmSciTech Source Type: research

Pulmonary and Regional Deposition of Nebulized and Dry Powder Aerosols in Ferrets.
Abstract The utilization of ferrets as a non-clinical model for disease is rapidly increasing within drug development. Many of these models include respiratory diseases that involve targeted drug delivery via nose-only inhalation. While the deposition patterns within other non-clinical models (mice, rats, canines, and non-human primates) have been well studied, the local and regional deposition of aerosols in ferrets has not been well characterized. Therefore, inhalation aerosols were developed, radiolabeled and the radiolabeling methods validated to support SPECT-CT imaging and quantification of regional depositi...
Source: AAPS PharmSciTech - July 1, 2019 Category: Drugs & Pharmacology Authors: Kuehl PJ, Chand R, McDonald JD, Hava DL, DeHaan WH Tags: AAPS PharmSciTech Source Type: research

Combination of UVB Absorbing Titanium Dioxide and Quercetin Nanogel for Skin Cancer Chemoprevention.
Abstract Sunscreens are widely prescribed and used to prevent skin cancer; however, they have been reported to contain various chemicals which mimic hormones and disrupt hormonal functioning in humans. The aim of this study was to develop topical nanogel for skin cancer prevention using an antioxidant compound quercetin (Qu) and inorganic titanium dioxide (TiO2). Two formulations of Qu nanocrystals were optimized with low and high concentration of drug using the Box-Behnken design with the quadratic response surface model and further homogenized with TiO2. Qu nanocrystal (0.08% and 0.12%) formulations showed a par...
Source: AAPS PharmSciTech - June 27, 2019 Category: Drugs & Pharmacology Authors: Bagde A, Patel K, Mondal A, Kutlehria S, Chowdhury N, Gebeyehu A, Patel N, Kumar N, Singh M Tags: AAPS PharmSciTech Source Type: research

Alginate Microspheres Elicit Innate M1-Inflammatory Response in Macrophages Leading to Bacillary Killing.
We examined the role of drug-free inhalable alginate microspheres (A-MS) on phagocytosis efficiency and subsequent immune cell activation in Escherichia coli-infected THP-1-derived macrophages. Alginate particles have been widely investigated as carriers for prolonged delivery of bioactive (i.e., drugs, diagnostics, and vaccines). A-MS were fabricated by industry scalable spray-congealing process using divalent cation-induced gelification. E. coli-infected macrophages (multiplicity of infection (MOI 1:10) were treated with drug-free A-MS, where we found a consistent moderate reduction in bacillary viability. Particles were...
Source: AAPS PharmSciTech - June 27, 2019 Category: Drugs & Pharmacology Authors: Vaghasiya K, Eram A, Sharma A, Ray E, Adlakha S, Verma RK Tags: AAPS PharmSciTech Source Type: research

Budesonide-Loaded Eudragit S 100 Nanocapsules for the Treatment of Acetic Acid-Induced Colitis in Animal Model.
Abstract Nanoparticles for colon-drug delivery were designed and evaluated to solve many discrepancy issues as insufficient drug amount at diseased regions, high adverse effects of released drugs, and unintentionally premature drug release to noninflamed gastrointestinal regions. Herein, the prepared budesonide-loaded Eudragit S 100/Capryol 90 nanocapsules for the treatment of inflammatory bowel disease. Nanocapsules were prepared efficiently by nanoprecipitation technique and composed mainly of the pH-sensitive Eudragit S 100 polymeric coat with a semisynthetic Capryol 90 oily core. Full 31 × ...
Source: AAPS PharmSciTech - June 26, 2019 Category: Drugs & Pharmacology Authors: Qelliny MR, Aly UF, Elgarhy OH, Khaled KA Tags: AAPS PharmSciTech Source Type: research

Correction to: Quantification of Inkjet-Printed Pharmaceuticals on Porous Substrates Using Raman Spectroscopy and Near-Infrared Spectroscopy.
Abstract Mohammed Al-Sharabi's affiliation was incorrect at the time of publishing. The updated affiliation appears below. PMID: 31243631 [PubMed - in process] (Source: AAPS PharmSciTech)
Source: AAPS PharmSciTech - June 26, 2019 Category: Drugs & Pharmacology Authors: Edinger M, Iftimi LD, Markl D, Al-Sharabi M, Bar-Shalom D, Rantanen J, Genina N Tags: AAPS PharmSciTech Source Type: research

Novel Application of Hot Melt Extrusion for the Manufacturing of Vaginal Films Containing Microbicide Candidate Dapivirine.
Abstract Polymeric films are safe and effective and can be used for vaginal administration of microbicide drug candidates. Dapivirine (DPV), an investigational and clinically advanced antiretroviral drug, was selected as a model compound for this study. We have previously developed and clinically tested a quick-dissolving DPV film using solvent cast (SC) manufacturing technique. As an alternative to current pharmaceutical film manufacturing techniques, we investigated hot melt extrusion (HME) process in this study because it has several benefits, including its capacity as a continuous manufacturing process, lack o...
Source: AAPS PharmSciTech - June 26, 2019 Category: Drugs & Pharmacology Authors: Regev G, Patel SK, Moncla BJ, Twist J, Devlin B, Rohan LC Tags: AAPS PharmSciTech Source Type: research

Effect of Formulation Variables on the Nasal Permeability and Stability of Naloxone Intranasal Formulations.
This study focuses on investigating the effect of formulation variables including choice of preservatives, stabilizer, and pH on the permeability and stability of naloxone IN formulations. The in vitro permeability of naloxone was evaluated employing EpiAirway™ tissue-mounted Ussing chambers. BKC was found to enhance the apparent permeability (Papp) of naloxone significantly (p 
Source: AAPS PharmSciTech - June 24, 2019 Category: Drugs & Pharmacology Authors: Hsu HJ, Yang Y, Pavuluri V, Abraham C, Naraharisetti SB, Ashraf M, Al-Ghabeish M Tags: AAPS PharmSciTech Source Type: research

Estimation of Anti-inflammatory and Analgesic Effects of Topical NANOCEN (Nanoliposomal Arthrocen) on Mice.
Abstract The purpose of this study was to evaluate the effect of topical application of nanoliposomal avocado/soybean unsaponifiables (NANOCEN) on inflammation inhibition and pain relief in mice. NANOCEN was prepared by the injection method and characterized for vesicle size, charge, entrapment efficiency, in vitro release, and 1-month vesicle stability. The analysis of ASU formulation showed that liposomes had an average size of around 146 nm with a surface charge of - 43 mV. SEM and TEM imaging confirmed the spherical shape of the nanovesicles in ASU formulation. Moreover, ASU nanoliposomes had ...
Source: AAPS PharmSciTech - June 24, 2019 Category: Drugs & Pharmacology Authors: Goudarzi R, Amini S, Dehpour AR, Partoazar A Tags: AAPS PharmSciTech Source Type: research

Flexibility of 3D Extruded Printing for a Novel Controlled-Release Puerarin Gastric Floating Tablet: Design of Internal Structure.
The objective of this study was to investigate the development of a novel puerarin gastric floating system with a concentric annular internal pattern by a 3D extrusion-based printing technique and to explore the flexibility of turning the release behavior through the design of the internal structure. The composition consisted of the conventional sustained-release pharmaceutical excipients without addition of foaming agent or light materials. First, the proper alcohol/water proportion was selected for the binding agent. The desired drug release behaviors and good floating properties were obtained either through modification...
Source: AAPS PharmSciTech - June 24, 2019 Category: Drugs & Pharmacology Authors: Li P, Zhang S, Sun W, Cui M, Wen H, Li Q, Pan W, Yang X Tags: AAPS PharmSciTech Source Type: research

Liqui-Pellet: the Emerging Next-Generation Oral Dosage Form Which Stems from Liquisolid Concept in Combination with Pelletization Technology.
Abstract In spite of the major advantages that the liquisolid technology offers, particularly in tackling poor bioavailability of poorly water-soluble drugs (i.e., BCS Class II drugs), there are a few critical drawbacks. The inability of a high liquid load factor, poor flowability, poor compactibility, and an inability to produce a high dose dosage form of a reasonable size for swallowing are major hurdles, hampering this technology from being commercially feasible. An attempt was therefore made to overcome these drawbacks whilst maintaining the liquisolid inherent advantages. This resulted in the emerging next ge...
Source: AAPS PharmSciTech - June 24, 2019 Category: Drugs & Pharmacology Authors: Lam M, Ghafourian T, Nokhodchi A Tags: AAPS PharmSciTech Source Type: research

Surface Wettability Modulated by Surfactant and Its Effects on the Drug Release and Absorption of Fenofibrate Solid Dispersions.
The objective of this study is to explore the surface wettability modulated by a surfactant and its effects on the drug release and absorption of fenofibrate solid dispersions (FF SDs). Both the polyvinylpyrrolidone/sodium lauryl sulfate (PVP/SLS) coprecipitate and FF SDs were prepared by solvent evaporation method. The contact angle of PVP/SLS coprecipitate with various PVP/SLS weight ratios was determined to screen out the suitable content of SLS incorporated in FF SDs. Scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS) was used to analyze the surface composition of the PVP/SLS coprecipitate, suggestin...
Source: AAPS PharmSciTech - June 24, 2019 Category: Drugs & Pharmacology Authors: Yang B, Wei C, Qian F, Li S Tags: AAPS PharmSciTech Source Type: research

Overview of Brazilian Requirements for Therapeutic Equivalence of Orally Inhaled and Nasal Drug Products.
Abstract Brazil has established a framework for provision of generic pharmaceuticals including for orally inhaled and nasal drug products (OINDP) to its populace. This includes the development of guidelines or "resolutions" and normative instructions describing the Brazilian medicines agency's (Anvisa) expectations for demonstrating OINDP therapeutic equivalence. The Anvisa regulatory framework for OINDP therapeutic equivalence, challenges, and comparisons with the US Food and Drug Administration and European Medicines Agency approaches are assessed and discussed. PMID: 31236849 [PubMed - in process...
Source: AAPS PharmSciTech - June 24, 2019 Category: Drugs & Pharmacology Authors: Silva MC, Costa HS, Valadares BN, Grecchi L, Nagao L, Santos GML Tags: AAPS PharmSciTech Source Type: research

Effect of Fast-Disintegrating Tablets' Characteristics on the Sublingual Permeability of Atropine Sulfate for the Potential Treatment of Organophosphates Toxicity.
Abstract Atropine sulfate (AS) fast-disintegrating sublingual tablets (FDSTs) were tested for AS sublingual permeation's feasibility as a potential alternative dosage form to treat organophosphates (OP) toxicity. More than 12,000 OP pesticide toxicity cases were reported in the USA from 2011 to 2014. AS is the recommended antidote for OP toxicity; however, it is only available as an ATROPEN® auto-injector, an IM injection, for self-administration, which is associated with several drawbacks and limitations. Six AS FDST batches were formulated and characterized. Two tablet sizes, group A weighing 150 mg and...
Source: AAPS PharmSciTech - June 21, 2019 Category: Drugs & Pharmacology Authors: Aodah A, Rawas-Qalaji M, Bafail R, Rawas-Qalaji M Tags: AAPS PharmSciTech Source Type: research

Evaluation of Abuse-Deterrent Characteristics of Tablets Prepared via Hot-Melt Extrusion.
In this study, the effect of formulation variables and process parameters on the abuse-deterrent (AD) characteristics of a matrix tablet manufactured using hot-melt extrusion (HME) was investigated. The formulation variables included polyethylene oxide (PEO) grades and its input level, while the HME process parameters varied were barrel temperature profile and die diameter. Depending on the diameter of the extrudate (2.5 mm or 5.0 mm), two different downstream processes were used to prepare the tablets: cryo-milling followed by compression for the 2.5 mm extrudate, and cutting followed by compression fo...
Source: AAPS PharmSciTech - June 21, 2019 Category: Drugs & Pharmacology Authors: Xu X, Siddiqui A, Srinivasan C, Mohammad A, Rahman Z, Korang-Yeboah M, Feng X, Khan M, Ashraf M Tags: AAPS PharmSciTech Source Type: research

Modification of Three-Phase Drug Release Mode of Octreotide PLGA Microspheres by Microsphere-Gel Composite System.
Abstract In order to obtain sustained release of biodegradable microspheres, the purpose of this study was to design and characterize an injectable octreotide microsphere-gel composite system. The octreotide microspheres were prepared by phase separation method, which used PLGA as a carrier material, dimethyl silicone oil as a phase separation reagent, and n-heptane-Span 80 as a hardener. In addition, we used poloxamer 407 (PL 407) and poloxamer 188 (PL 188) as the thermosensitive gel matrix material. The composite system was obtained by scattering octreotide microspheres in a poloxamer gel. In vitro data showed t...
Source: AAPS PharmSciTech - June 21, 2019 Category: Drugs & Pharmacology Authors: Wang T, Zhang C, Zhong W, Yang X, Wang A, Liang R Tags: AAPS PharmSciTech Source Type: research

Investigation of Controlled Release Molecular Mechanism of Oil Phase in Spilanthol Emulsion: Development and In Vitro, In Vivo Characterization.
In conclusion, an effective emulsion was developed and the controlled release effect of oil phase was proved through drug-excipient interaction. PMID: 31222590 [PubMed - in process] (Source: AAPS PharmSciTech)
Source: AAPS PharmSciTech - June 20, 2019 Category: Drugs & Pharmacology Authors: Yang D, Li W, Fang L, Liu C Tags: AAPS PharmSciTech Source Type: research

Crystal Transformation of β-CD-MOF Facilitates Loading of Dimercaptosuccinic Acid.
Crystal Transformation of β-CD-MOF Facilitates Loading of Dimercaptosuccinic Acid. AAPS PharmSciTech. 2019 Jun 18;20(6):224 Authors: Xiong Y, Wu L, Guo T, Wang C, Wu W, Tang Y, Xiong T, Zhou Y, Zhu W, Zhang J Abstract The β-cyclodextrin-metal-organic framework (β-CD-MOF), a potential drug delivery carrier, presents a densely packed laminated crystal structure (CCDC number 1041782) that prevents drug from entering inside the molecular voids in most CD units. In this paper, it was demonstrated that dimercaptosuccinic acid (DMSA), an instable small molecule chemical drug, was successfully ...
Source: AAPS PharmSciTech - June 18, 2019 Category: Drugs & Pharmacology Authors: Xiong Y, Wu L, Guo T, Wang C, Wu W, Tang Y, Xiong T, Zhou Y, Zhu W, Zhang J Tags: AAPS PharmSciTech Source Type: research

Mucoadhesive In Situ Gelling Liquid Crystalline Precursor System to Improve the Vaginal Administration of Drugs.
lli M Abstract The vaginal mucosa is a very promising route for drug administration due to its high permeability and the possibility to bypass first pass metabolism; however, current vaginal dosage forms present low retention times due to their dilution in vaginal fluids, which hampers the efficacy of many pharmacological treatments. In order to overcome these problems, this study proposes to develop a mucoadhesive in situ gelling liquid crystalline precursor system composed of 30% of oleic acid and cholesterol (7:1), 40% of ethoxylated and propoxylated cetyl alcohol, and 30% of a dispersion of 16% Poloxamer 407. ...
Source: AAPS PharmSciTech - June 18, 2019 Category: Drugs & Pharmacology Authors: de Araújo PR, Calixto GMF, da Silva IC, de Paula Zago LH, Oshiro Junior JA, Pavan FR, Ribeiro AO, Fontana CR, Chorilli M Tags: AAPS PharmSciTech Source Type: research

Formulation of Dronedarone Hydrochloride-Loaded Proliposomes: In Vitro and In Vivo Evaluation Using Caco-2 and Rat Model.
The objective of the present study was to develop a proliposomal formulation to increase the oral bioavailability of dronedarone hydrochloride (dronedarone HCl) by enhancing solubility, dissolution, and/or intestinal absorption. Proliposomes were prepared by using solvent evaporation method. In this process, different ratios of drug, phospholipids, such as soy phosphatidylcholine (SPC), Phospholipon 90H, hydrogenated egg phosphatidylcholine (HEPC), and dimyristoyl phosphatidylglycerol (DMPG), and cholesterol were used. Physical characterization and in vitro dissolution studies were evaluated for the prepared formulations. ...
Source: AAPS PharmSciTech - June 18, 2019 Category: Drugs & Pharmacology Authors: Kovvasu SP, Kunamaneni P, Yeung S, Rueda J, Betageri GV Tags: AAPS PharmSciTech Source Type: research

Decision Support for Excipient Risk Assessment in Pharmaceutical Manufacturing.
Abstract Excipients have always been a key input into pharmaceutical products, profoundly affecting product quality. Currently, most of our knowledge of excipient critical quality attributes is empirical, gained through experience, and shared through publications and other sources. The behavior of excipients is complicated, with many different failure modes that depend on the type of dosage form. Even within the same dosage form, there can be multiple failure modes depending on the manufacturing method. This complex behavior creates many possible combinations to assess when designing a formulation or evaluating re...
Source: AAPS PharmSciTech - June 18, 2019 Category: Drugs & Pharmacology Authors: Bejarano A, Hewa Nadungodage C, Wang F, Catlin AC, Hoag SW Tags: AAPS PharmSciTech Source Type: research

Prediction of Human Pharmacokinetics of Fomepizole from Preclinical Species Pharmacokinetics Based on Normalizing Time Course Profiles.
Abstract Fomepizole is used as an antidote to treat methanol poisoning due to its selectivity towards alcohol dehydrogenase. In the present study, the goal is to develop a method to predict the fomepizole human plasma concentration versus time profile based on the preclinical pharmacokinetics using the assumption of superimposability on simulated time course profiles of animals and humans. Standard allometric equations with/without correction factors were also assimilated in the prediction. The volume of distribution at steady state (Vss) predicted by simple allometry (57.55 L) was very close to the reported ...
Source: AAPS PharmSciTech - June 18, 2019 Category: Drugs & Pharmacology Authors: Jairam RK, Mallurwar SR, Sulochana SP, Chandrasekhar DV, Todmal U, Bhamidipati RK, Richter W, Srinivas NR, Mullangi R Tags: AAPS PharmSciTech Source Type: research

Prediction of Dissolution of Sustained Release Coated Ciprofloxacin Beads Using Near-infrared Spectroscopy and Process Parameters: a Data Fusion Approach.
Abstract The aim of the work is to develop a data fusion model using near-infrared (NIR) and process parameters for the predictions of drug dissolution from controlled release multiparticulate beads. Using a design of experiments, ciprofloxacin-coated beads were manufactured and critical process parameters such as air volume, product temperature, curing temperature, and curing time were measured; environmental humidity was monitored using a Pyrobuttons®. The NIR spectra were decomposed using principal component analysis (PCA). The PCA scores were fused with process measurements and all variables were auto...
Source: AAPS PharmSciTech - June 18, 2019 Category: Drugs & Pharmacology Authors: Ibrahim A, Kothari BH, Fahmy R, Hoag SW Tags: AAPS PharmSciTech Source Type: research

Novel Hot Melt Extruded Matrices of Hydroxypropyl Cellulose and Amorphous Felodipine-Plasticized Hydroxypropyl Methylcellulose as Controlled Release Systems.
Abstract Hydroxypropyl methylcellulose (HPMC) is a hydrophilic retarding-release polymer with the limited application in hot melt extrusion (HME) due to its high glass transition temperature (Tg 181-191°C) and melt viscosity. The aim of this study is to develop hot melt extruded matrices using hydroxypropyl cellulose (HPC) and felodipine (FLDP) with HPMC for controlled release and explore the relations of their specialty, processability, and structure with the product properties. Results showed that FLDP/HPCEF/HPMC can be extruded at 160°C with torques not more than 0.5 N·m. The extruded matric...
Source: AAPS PharmSciTech - June 14, 2019 Category: Drugs & Pharmacology Authors: Yi S, Wang J, Lu Y, Ma R, Gao Q, Liu S, Xiong S Tags: AAPS PharmSciTech Source Type: research

Delivery of Docetaxel to Brain Employing Piperine-Tagged PLGA-Aspartic Acid Polymeric Micelles: Improved Cytotoxic and Pharmacokinetic Profiles.
In this study, poly-(lactic-co-glycolic) acid (PLGA) was conjugated with aspartic acid and was characterized by nuclear magnetic resonance and Fourier transform infrared spectroscopy. Docetaxel-loaded polymeric micelles were prepared, and piperine was tagged. The neuroblastoma cytotoxicity studies revealed a substantially higher cytotoxic potential of the developed system to that of plain docetaxel, which was further corroborated by cellular uptake employing confocal laser scanning microscopy. The hemocompatible system was able to enhance the pharmacokinetic profile in terms of 6.5-fold increment in bioavailability followe...
Source: AAPS PharmSciTech - June 14, 2019 Category: Drugs & Pharmacology Authors: Singh A, Thotakura N, Singh B, Lohan S, Negi P, Chitkara D, Raza K Tags: AAPS PharmSciTech Source Type: research

Enhancement of Oral Bioavailability and Anti-hyperuricemic Activity of Isoliquiritigenin via Self-Microemulsifying Drug Delivery System.
Abstract The aim of this study was to develop a self-microemulsifying drug delivery system (SMEDDS) for enhancement of the oral bioavailability of isoliquiritigenin (ISL) as well as evaluate its in vivo anti-hyperuricemic effect in rats. The ISL-loaded self-microemulsifying drug delivery system (ISL-SMEDDS) was comprised of ethyl oleate (EO, oil phase), Tween 80 (surfactant), and PEG 400 (co-surfactant). The ISL-SMEDDS exhibited an acceptable narrow size distribution (44.78 ± 0.35 nm), negative zeta potential (- 10.67 ± 0.86 mV), and high encapsulation eff...
Source: AAPS PharmSciTech - June 11, 2019 Category: Drugs & Pharmacology Authors: Zhang K, Wang Q, Yang Q, Wei Q, Man N, Adu-Frimpong M, Toreniyazov E, Ji H, Yu J, Xu X Tags: AAPS PharmSciTech Source Type: research

Correction to: Nondestructive Quantitative Inspection of Drug Products Using Benchtop NMR Relaxometry-the Case of NovoMix ® 30.
Correction to: Nondestructive Quantitative Inspection of Drug Products Using Benchtop NMR Relaxometry-the Case of NovoMix® 30. AAPS PharmSciTech. 2019 Jun 06;20(5):214 Authors: Briggs KT, Taraban MB, Wang W, Yu YB Abstract Typesetting error occurred and author corrections to the equations and text edits at the proofing stage were not incorporated in the published article. The original article has been corrected. PMID: 31172314 [PubMed - in process] (Source: AAPS PharmSciTech)
Source: AAPS PharmSciTech - June 6, 2019 Category: Drugs & Pharmacology Authors: Briggs KT, Taraban MB, Wang W, Yu YB Tags: AAPS PharmSciTech Source Type: research

Quality by Design Enabled Development of Oral Self-Nanoemulsifying Drug Delivery System of a Novel Calcimimetic Cinacalcet HCl Using a Porous Carrier: In Vitro and In Vivo Characterisation.
Abstract In this present research, work quality by design-enabled development of cinacalcet HCl (CH)-loaded solid self-nanoemulsifying drug delivery system (S-SNEDDS) was conducted using a porous carrier in order to achieve immediate drug release and better oral bioavailability. Capmul MCM (CAP), Tween 20 (TW 20) and Transcutol P (TRP) were selected as excipients. Cumulative % drug release at 30 min (Q30), emulsification times (ET), mean globule size (GS) and polydispersity index (PDI) were identified as critical quality attributes (CQAs). Factor mode effect analysis (FMEA) and Taguchi screening design were a...
Source: AAPS PharmSciTech - June 6, 2019 Category: Drugs & Pharmacology Authors: Panigrahi KC, Patra CN, Rao MEB Tags: AAPS PharmSciTech Source Type: research

Isolation of Itraconazole Nanostructured Microparticles via Spray Drying with Rational Selection of Optimum Base for Successful Reconstitution and Compaction.
Abstract The addition of matrix formers within a formulation provides a means for enhancing the redispersibility of nanoparticles (NPs) enabling them to retain their advantageous properties imparted onto them by their sub-micron size. In this work, NPs were isolated in the solid state via spray drying with a range of sugars. The processed powders were characterized, establishing that itraconazole (ITR) nanostructured microparticles (NMPs) spray dried in the presence of mannitol and trehalose had favorable redispersibility confirmed by dynamic light scattering and nanoparticle tracking analysis. Solid-state analysi...
Source: AAPS PharmSciTech - June 6, 2019 Category: Drugs & Pharmacology Authors: McComiskey KPM, McDonagh A, Tajber L Tags: AAPS PharmSciTech Source Type: research

Fabrication of Dissolvable Microneedle Patches Using an Innovative Laser-Cut Mould Design to Shortlist Potentially Transungual Delivery Systems: In Vitro Evaluation.
We report the design of MN patch mould using a laser-cutting machine and solvent casting of several hydrophilic polymers to fabricate these MN patches. Formulations were evaluated for their in vitro release and penetration properties and selected based on physical characterization for compatibility (differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD)), dimension repeatability and drug content uniformity. A 72-array of cone-shaped MN patch mould was successfully constructed on polymethylmethacrylate sheets. Interval and frequency of laser exposure were pivotal to determine the needle sharpness, attai...
Source: AAPS PharmSciTech - June 6, 2019 Category: Drugs & Pharmacology Authors: Albarahmieh E, AbuAmmouneh L, Kaddoura Z, AbuHantash F, Alkhalidi BA, Al-Halhouli A Tags: AAPS PharmSciTech Source Type: research

Temperature/pH-Triggered PNIPAM-Based Smart Nanogel System Loaded With Anastrozole Delivery for Application in Cancer Chemotherapy.
This study investigates the formulation optimization anastrozole (ANST)-loaded PNIPAM nanoparticle (NPs) prepared by solvent evaporation method for pH- and thermo-responsive drug delivery. Box-Behnken design (BBD) was implemented to observe the effect of selected process parameters on quality attributes product including particle size 110.15 nm, zeta potential - 11.02 mV, PDI 0.175, and drug loading 8.35% (DL). The statistical data was found to fit in the quadratic model and p value is less than 0.005. The thermo-responsive behavior of PNIPAM is evaluated on DLS and UV-Visible spectroscopy at elevated temp...
Source: AAPS PharmSciTech - June 4, 2019 Category: Drugs & Pharmacology Authors: Singh A, Vaishagya K, K Verma R, Shukla R Tags: AAPS PharmSciTech Source Type: research

A Novel Surfactant-Free O/O Paclitaxel Ointment for the Topical Treatment of Psoriasis.
Abstract Psoriasis is an autoimmune disorder disease with pink-colored plaques and excessive proliferation which is hard to be cured completely. The study focuses on the anti-psoriatic efficacy of O/O paclitaxel ointment which can promote the assembly of microtubules and lead to death of overproliferation cells of the psoriasis epidermal. A high-speed shearing method was adopted in preparing the ointment, in which propylene carbonate was used as the internal oil phase to solve paclitaxel completely. It was characterized by the appearance, particle size, rheological behavior, and in vitro release. The amount of pac...
Source: AAPS PharmSciTech - June 4, 2019 Category: Drugs & Pharmacology Authors: Yin X, Cao X, Li J, Cheng X, Cheng G, Zou M, Piao H Tags: AAPS PharmSciTech Source Type: research

Designing of a pH-Triggered Carbopol ®/HPMC In Situ Gel for Ocular Delivery of Dorzolamide HCl: In Vitro, In Vivo, and Ex Vivo Evaluation.
In this study, a 32 full factorial design was used for preparation of in situ gel formulations using different levels of Carbopol® and hydroxyl propyl methyl cellulose (HPMC). Rheological behavior, in vitro drug release, ex vivo corneal permeability, and IOP-lowering activity were investigated. DRZ solution (2% w/v) containing of 0.1% (w/v) Carbopol® and 0.1% (w/v) HPMC was selected as the optimal formulation considering its free flow under non-physiological conditions (initial pH and 25 ± 2°C) and transition to appropriate gel form under physiological circumstance (pH 7.4 and 34°C...
Source: AAPS PharmSciTech - June 3, 2019 Category: Drugs & Pharmacology Authors: Kouchak M, Mahmoodzadeh M, Farrahi F Tags: AAPS PharmSciTech Source Type: research

In Memoriam: Dr. Paul B. Myrdal.
PMID: 31161303 [PubMed - in process] (Source: AAPS PharmSciTech)
Source: AAPS PharmSciTech - June 3, 2019 Category: Drugs & Pharmacology Authors: Kuehl PJ, Smyth HD, Stein SW, Williams RO Tags: AAPS PharmSciTech Source Type: research

A Thermodynamic Balance Model for Liquid Film Drying Kinetics of a Tablet Film Coating and Drying Process.
Abstract A tablet film coating and drying process was assessed by an experimentally validated thermodynamic balance model. Mass conservation equations were derived for the process air and the aqueous coating solution. Thermodynamic behavior of the solution was described by evaporation at the tablet surface and penetration into the tablet. Energy balance equations including heat loss to the atmosphere were coupled to the mass conservation equation. Experimental data using the ConsiGma™ coater (GEA, Belgium) were used for both parameter estimation and model validation. The results showed the proposed model can...
Source: AAPS PharmSciTech - June 3, 2019 Category: Drugs & Pharmacology Authors: Cha B, Galbraith SC, Liu H, Park SY, Huang Z, O'Connor T, Lee S, Yoon S Tags: AAPS PharmSciTech Source Type: research

Quantification of Inkjet-Printed Pharmaceuticals on Porous Substrates Using Raman Spectroscopy and Near-Infrared Spectroscopy.
In conclusion, NIR and Raman spectroscopic techniques could be used complementary as fast API quantification tools for inkjet-printed medicines. PMID: 31161397 [PubMed - in process] (Source: AAPS PharmSciTech)
Source: AAPS PharmSciTech - June 3, 2019 Category: Drugs & Pharmacology Authors: Edinger M, Iftimi LD, Markl D, Al-Sharabi M, Bar-Shalom D, Rantanen J, Genina N Tags: AAPS PharmSciTech Source Type: research

A High-Demanding Strategy to Ensure the Highest Quality Standards of Oral Liquid Individualized Medicines for Pediatric Use.
In this study, a general high-demanding strategy was elaborated to validate oral liquid dosage forms, including validation of the analytical method used to test their quality. A second part focuses on the elaboration of liquid formulations for pediatrics with the highest standards of quality taking into account CQAs that were not contemplated by official compendial such as content uniformity and physical stability. PMID: 31161450 [PubMed - in process] (Source: AAPS PharmSciTech)
Source: AAPS PharmSciTech - June 3, 2019 Category: Drugs & Pharmacology Authors: Suárez-González J, Santoveña-Estévez A, Armijo-Ruíz S, Castillo A, Fariña JB Tags: AAPS PharmSciTech Source Type: research

Determination of Passive Dry Powder Inhaler Aerodynamic Particle Size Distribution by Multi-Stage Cascade Impactor: International Pharmaceutical Aerosol Consortium on Regulation & Science (IPAC-RS) Recommendations to Support Both Product Quality Control and Clinical Programs.
This article provides recommendations for achieving consistent APSD measurements, including selection of the CI, pre-separator, and flow control equipment, as well as reviewing considerations that relate to the shape of the flow rate-sampling time profile. Evidence from comparisons of different DPIs delivering the same active pharmaceutical ingredients (APIs) is indicative that the compendial method for APSD measurement is insensitive as a predictor of pharmacokinetic outcomes. Although inappropriate for product quality testing, guidance is therefore provided towards adopting a more clinically realistic methodology, includ...
Source: AAPS PharmSciTech - May 30, 2019 Category: Drugs & Pharmacology Authors: Mitchell JP, Stein SW, Doub W, Goodey AP, Christopher JD, Patel RB, Tougas TP, Lyapustina S Tags: AAPS PharmSciTech Source Type: research