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Acceleration of new medicines–CMC lessons learned from emergency use authorizations AAPS Open Pub Date : 2024-03-04 James Bernstein, Kim Huynh-Ba, Patrick Lynch, Thomas Oliver, Reza Oliyai, Scott W. Roberts, Andrea Schirmer, David Schwinke, Kin Tang, Jessica Ursin
The American Association of Pharmaceutical Scientists (AAPS) Chemistry, Manufacturing, and Control (CMC) Community hosted a virtual panel discussion on July 15, 2022, to provide a forum to discuss industry and regulator CMC challenges associated with emergency use authorizations.
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Observation of antitumor mechanism of GE11-modified paclitaxel and curcumin liposomes based on cellular morphology changes AAPS Open Pub Date : 2024-02-08 Hailing Tang, Lijuan Li, Baoshan Wang
Curcumin and paclitaxel are widely used as anti-tumor hydrophobic model drugs for the designation of smart tumor-targeting nanocarriers and the study of the correlation between structural characteristics of nanoparticles and in vivo therapeutic efficacy. Various signaling pathways on cell growth and proliferation have been comprehensively studied in vitro and in vivo under the action of curcumin and
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Enhancement of material attributes of poorly compressible metformin hydrochloride through coprocessing with hydroxypropyl cellulose (HPC-L) using coprecipitation (CPT) AAPS Open Pub Date : 2023-11-06 Kaushalendra Chaturvedi, Pasaorn Pongkulapa, Xiaoyi Ding, Harsh S. Shah, San Kiang, Veeran Kadajji
Coprocessing involves integration of multiple substances to improve the physical, chemical, mechanical, and biopharmaceutical properties of a material. Coprocessing is a promising technique in the pharmaceutical industry which support both drug substance and drug product processes. When active pharmaceutical ingredients (APIs) are coprocessed with excipients, it can enable direct compression and continuous
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Utility of in vitro release testing (IVRT) to assess ‘sameness’ of 1% clotrimazole creams for use as a biowaiver AAPS Open Pub Date : 2023-11-01 Hannah Wellington, Seeprarani Rath, Sagaran Abboo, Isadore Kanfer
The October 2022 draft United States Food and Drug Administration (FDA) guidance presents an option of in vitro release test (IVRT) studies as a biowaiver for topical drug products submitted in abbreviated new drug applications (ANDAs). However, the product-specific guidance (PSG) for 1% clotrimazole (CLZ) topical cream does not provide an in vitro option for biowaiver and requires a clinical endpoint
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Self-microemulsifying system of an ethanolic extract of Heliopsis longipes root for enhanced solubility and release of affinin AAPS Open Pub Date : 2023-10-16 Dailenys Marrero-Morfa, César Ibarra-Alvarado, Francisco J. Luna-Vázquez, Miriam Estévez, Eremy Miranda Ledesma, Alejandra Rojas-Molina, Carlos T. Quirino-Barreda
Self-microemulsifying or self-nanoemulsifying drug delivery systems (SMEDDS/SNEDDS) are well known to improve the dissolution and increase the oral bioavailability of hydrophobic drugs, including herbal extracts. Organic extracts of Heliopsis longipes root and affinin, its main component, induce a vasodilator effect; however, they are poorly water soluble and therefore are difficult to administer and
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Preparation, characterization, and biological activity of the inclusion complex of dihydroquercetin and β-Cyclodextrin AAPS Open Pub Date : 2023-10-03 Yaping Xu, Yue Wang, Chujie Li, Tao Han, Haiming Chen, Wenxue Chen, Qiuping Zhong, Jianfei Pei, Guido R. M. M. Haenen, Zhengwen Li, Mohamed Moalin, Ming Zhang, Weijun Chen
Dihydroquercetin (DHQ) is a natural occurring dihydroflavonol that has strong antioxidant and antibacterial activities. However, its application is limited due to its poor solubility. This study aims to improve the aqueous solubility of DHQ by complexing DHQ with β-cyclodextrin (β-CD) to boost its biological activity. DHQ was encapsulated with β-CD by freeze drying at a 1:1-M ratio. The structure of
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Bioequivalence clinical trial simulation: a case study of apalutamide administered in applesauce versus whole tablets AAPS Open Pub Date : 2023-08-07 Alex Yu, Oliver Ackaert
Patients who have difficulty swallowing apalutamide tablets may benefit from administration in a food vehicle that is easier to swallow. In a previous single-dose study conducted in healthy male volunteers (n = 12) a larger peak exposure was observed (+ 27.6%) for apalutamide in applesauce compared with whole tablets, despite a comparable extent of exposure (+ 5%). However, because apalutamide is taken
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Compatibility study of patiromer with juices/liquids and soft foods AAPS Open Pub Date : 2023-08-01 Martin Khoeiklang, Maria Wilhelm, Lingyun Li, Carol P. Moreno Quinn
Patiromer powder for oral suspension (patiromer o.s.) is a once-daily, potassium (K+) binder approved for the treatment of hyperkalemia. It is known that patiromer o.s. can be mixed with water, apple juice, or cranberry juice. This in vitro study assessed whether mixing patiromer o.s. with a variety of other liquids and soft foods would affect the total K+-exchange capacity (TKEC) of patiromer. Juices
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A review on lipid-based nanocarriers mimicking chylomicron and their potential in drug delivery and targeting infectious and cancerous diseases AAPS Open Pub Date : 2023-07-03 Rana E. Elnady, Maha M. Amin, Mohamed Y. Zakaria
Infectious and cancerous diseases are tedious to manage. The problem of drug resistance is often associated with anti-microbial and anti-cancer agents and is one of the most significant challenges that restrict their activity. Therefore, it is necessary to increase doses or drug combinations. However, introducing drugs in this way is often ineffective due to poor solubility, low bioavailability, reduced
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PEGylated magnetic nanographene oxide for targeted delivery of arsenic trioxide and sec-o-glucosylhamaudol in tumor treatment with improved dual-drugs synergistic effect AAPS Open Pub Date : 2023-06-05 Jinlai Cheng, Kun Hong, Jianhui Sun, Hongmei Li, Yu Zhao, Qinghe Zhao, Yuqing Tan, Miyi Yang
Arsenic trioxide (ATO) is a promising chemotherapeutic agent, but its clinical application is limited due to its poor pharmacokinetics and dose-limited toxicity. Moreover, the combination of ATO and sec-o-glucosylhamaudol (SOG) can improve the therapeutic effect of hepatoma. In this study, PEGylated magnetic nanographene oxide (PEG@MGO) was used as magnetic carriers to enhance the targeting ability
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Structured content and data management—enhancing acceleration in drug development through efficiency in data exchange AAPS Open Pub Date : 2023-05-08 Jill Beierle, Marquerita Algorri, Marisol Cortés, Nina S. Cauchon, Andrew Lennard, J. Paul Kirwan, Shirley Oghamian, Michael J. Abernathy
Innovation in pharmaceutical therapeutics is critical for the treatment of serious diseases with unmet medical need. To accelerate the approval of these innovative treatments, regulatory agencies throughout the world are increasingly adopting the use of expedited pathways and collaborative regulatory reviews. These pathways are primarily driven by promising clinical results but become challenging for
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Stability considerations for drug-device combination products-21 CFR part 4 update AAPS Open Pub Date : 2023-05-01 Christopher Latoz, Laure Larkin, Kim Huynh-Ba
Combination products are therapeutic and diagnostic products that include two or more of the following: drug, biologic, and device. These products are needed for enhanced clinical outcomes and have more than one Mode of Action (MOA). Therefore, they require a more complex regulatory pathway and compliance with a minimum of two (2) sets of regulatory standards. In 2013, the 21 Code of Federal Regulations
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Extraction of niclosamide from commercial approved tablets into aqueous buffered solution creates potentially approvable oral and nasal sprays against COVID-19 and other respiratory infections AAPS Open Pub Date : 2023-04-14 David Needham
The low solubility, weak acid drug, niclosamide is a host cell modulator with broad-spectrum anti-viral cell-activity against many viruses, including stopping the SARS-CoV-2 virus from infecting cells in cell culture. As a result, a simple universal nasal spray preventative was proposed and investigated in earlier work regarding the dissolution of niclosamide into simple buffers. However, starting
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Strategies to stabilize dalbavancin in aqueous solutions: Section 4—identification of heat degradation products in 2-hydroxypropyl-β-cyclodextrin and divalent metal ion solutions at pH 4.5 and 7.0 AAPS Open Pub Date : 2023-04-04 Sardar M. Jakaria, David E. Budil, James Murtagh
Heat stress studies have been conducted in support of developing a heat-stable liquid solution of dalbavancin. The degradation products that form in heat-stressed buffered dalbavancin solutions have been identified, including the known major degradation product, mannosyl aglycone (MAG), and four previously uncharacterized compounds. Liquid chromatography-mass spectrometry/mass spectrometry (LC–MS/MS)
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Transdermal drug delivery system of lidocaine hydrochloride based on dissolving gelatin/sodium carboxymethylcellulose microneedles AAPS Open Pub Date : 2023-04-03 Shabnam Bahmani, Ramin Khajavi, Morteza Ehsani, Mohammad Karim Rahimi, Mohammad Reza Kalaee
In this study, it was aimed to introduce a transdermal drug delivery system with dissolving microneedles (DMNs) based on gelatin (GEL) and sodium carboxymethyl cellulose (NaCMC) for lidocaine hydrochloride (LidoHCl) delivery. Different ratios of GEL and NaCMC were mixed, loaded with an active agent of LidoHCl, and treated with glutaraldehyde (GTA) as a crosslinker agent. Prepared hydrogels were cast
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CMC development of [14C]-labeled sotorasib for the conduct of microtracer human ADME study AAPS Open Pub Date : 2023-03-20 Sonika Sharma, Prashant Agarwal, Andrew T. Parsons, James E. Huckle, Tiffany L. Correll
Human absorption, distribution, metabolism, and excretion (hADME) studies of new drugs are required for global regulatory filings. Recent advances in high sensitivity analytical technologies have enabled microtracer hADME studies wherein very low radioactive doses can be administered to healthy volunteers to study drug pharmacokinetic profile. Microtracer hADME studies are advantageous to accelerate
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Development of human-machine language interfaces for the visual analysis of complex biologics and RNA modalities and associated experimental data AAPS Open Pub Date : 2023-03-01 Roxanne K. Kunz, Atipat Rojnuckarin, Christian Marc Schmidt, Les P. Miranda
The advent of recombinant protein-based therapeutic agents in the 1980s and subsequent waves of innovation in molecular biology and engineering of biologics has permitted the production of an increasingly broad array of complex, high molecular weight constructs. While this has opened a powerful new toolbox of molecular scaffolds with which to probe and interdict biological processes, it also makes
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Simple and rapid method for analysis of urinary vancomycin using solid phase extraction and fluorescence spectroscopy AAPS Open Pub Date : 2023-02-06 Yuki Oshima, Mizuki Hori, Miyu Matsumoto, Masaru Kato
Vancomycin (VCM) is an antimicrobial that is recommended for therapeutic drug monitoring (TDM) for maintaining the efficacy and safety of treatment. The trough monitoring has been used to guide VCM dosing regimens. However, newer guidelines recommend the use of area under the curve/minimum inhibitory concentration (AUC/MIC)-guided vancomycin dosing, and there is a need for easier and more frequent
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Incorporating random effects in biopharmaceutical control strategies AAPS Open Pub Date : 2023-02-01 Thomas Oberleitner, Thomas Zahel, Marco Kunzelmann, Judith Thoma, Christoph Herwig
Random effects are often neglected when defining the control strategy for a biopharmaceutical process. In this article, we present a case study that highlights the importance of considering the variance introduced by random effects in the calculation of proven acceptable ranges (PAR), which form the basis of the control strategy. Linear mixed models were used to model relations between process parameters
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Customer-centric product presentations for monoclonal antibodies AAPS Open Pub Date : 2023-01-23 Beate Bittner
Delivering customer-centric product presentations for biotherapeutics, such as monoclonal antibodies (mAbs), represents a long-standing and paramount area of engagement for pharmaceutical scientists. Activities include improving experience with the dosing procedure, reducing drug administration-related expenditures, and ultimately shifting parenteral treatments outside of a controlled healthcare institutional
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Research on Pickering emulsification technology based on the concept of “combination of medicine and adjuvant” to improve the pH stability of volatile oil in solid preparations—taking Lingzhu Pulvis as an Example AAPS Open Pub Date : 2023-01-10 Peng, Lei, Wang, Mei, Zhang, Xiao-Fei, Guo, Dong-Yan, Zhai, Bing-Tao, Zou, Jun-Bo, Shi, Ya-Jun
Lingzhu Pulvis are widely used in clinical practice because of their therapeutic effects, but their stability and efficacy are affected by the easy oxidation and volatility of Acorus calamus. In this study, we combined the idea of “combination of medicine and adjuvant” and introduced Pickering emulsion technology to use the ingredients of Lingzhu Pulvis as the stabilizer of Pickering emulsion. Pearl
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Glycopeptide antibiotic drug stability in aqueous solution AAPS Open Pub Date : 2022-12-12 Jakaria, Sardar M., Budil, David E., Murtagh, James
Glycopeptide antimicrobials are a class of naturally occurring or semi-synthetic glycosylated products that have shown antibacterial activity against gram-positive organisms by inhibiting cell-wall synthesis. In most cases, these drugs are prepared in dry powder (lyophilized) form due to chemical and physical instability in aqueous solution; however, from an economic and practical point of view, liquid
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Meeting report: Advancing accelerated regulatory review with Real-Time Oncology Review (RTOR), Project Orbis, and the Product Quality Assessment Aid AAPS Open Pub Date : 2022-12-05 Algorri, Marquerita, Acharya, Ajay, Bernstein, James, Cauchon, Nina S., Chen, Xiao Hong, Huynh-Ba, Kim, Krantz, Carol, Li, Tao, Li, Yiwei, McLamore, Sherita, Roberts, Scott W., Schwinke, David, Shah, Rakhi, Schirmer, Andrea, Strickland, Helen, Tang, Kin, Watson, Timothy
The American Association of Pharmaceutical Scientists (AAPS) Chemistry, Manufacturing, and Controls (CMC) Community hosted two virtual panel discussions focusing on several novel regulatory review pathways for innovative oncology products: Real-Time Oncology Review (RTOR), Project Orbis, and the Product Quality Assessment Aid (PQAAid). The panel sessions were held on August 27, 2021, for the discussion
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Verification of nanoparticle formation, skin permeation, and apoptosis using nobiletin as a methoxyflavonoid derivative AAPS Open Pub Date : 2022-11-28 Inoue, Yutaka, Ishizawa, Moe, Itakura, Shoko, Tanikawa, Takashi, Todo, Hiroaki
Nobiletin (NOB), a polymethoxyflavonoid, is known for its antioxidant and anti-inflammatory effects and has antitumor activity. However, its poor solubility and low bioavailability pose a significant challenge in its delivery. In this experiment, NOB was added to Soluplus® (Sol)/l-ascorbyl 2,6-dipalmitate (ASC-DP) as a ternary system, and Sol/ASC-DP/NOB nanoparticles were obtained using the hydration
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Formulation mitigations for particle formation induced by enzymatic hydrolysis of polysorbate 20 in protein-based drug products: insights from a full-factorial longitudinal study AAPS Open Pub Date : 2022-11-14 Yuk, Inn H., Koulis, Theo, Doshi, Nidhi, Gregoritza, Kathrin, Hediger, Constanze, Lebouc-Haefliger, Vanessa, Giddings, Jamie, Khan, Tarik A.
Hydrolytic degradation of the polysorbate 20 (PS20) surfactant in protein-based liquid formulations releases free fatty acids (FFAs), which can accumulate to form particles in drug products during real-time (long-term) storage. To identify formulation conditions that mitigate the risk of particle formation, we conducted a longitudinal study using purified recombinant monoclonal antibody (mAb) formulated
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Results from in vitro and in vivo studies evaluating the bioavailability, effects of food, and administration as crushed tablet suspension on vericiguat pharmacokinetics AAPS Open Pub Date : 2022-11-01 Becker, Corina, Boettcher, Michael, Muenster, Uwe, Loewen, Stephanie, Lobmeyer, Maximilian, Mueck, Wolfgang
This article describes in vitro and in vivo studies that aimed to further characterize the biopharmaceutical properties and pharmacokinetic (PK) profile of vericiguat and to guide dosing recommendations. Five open-label, phase I studies characterized the biopharmaceutical aspects of vericiguat, including absolute bioavailability, bioavailabilities of different formulations, dose proportionality, and
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Stability of levothyroxine tablets in blister packaging versus bottles and vials under simulated in-use conditions AAPS Open Pub Date : 2022-10-10 Chun, Jonathan
Levothyroxine, the standard-of-care treatment for hypothyroidism, is susceptible to degradation when exposed to light and moisture and is an FDA-designated narrow therapeutic index drug. In this report, we examined how different packaging (e.g., cold form blister packs, manufacturer’s bottles, or pharmacy amber vials) affects the physicochemical integrity and potency of levothyroxine in conditions
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Technical transfer and commercialisation of lyophilised biopharmaceuticals — application of lyophiliser characterisation and comparability AAPS Open Pub Date : 2022-09-01 Cullen, Sean, Walsh, Emma, Gervasi, Valeria, Khamar, Dikshitkumar, McCoy, Timothy R.
A holistic approach was taken to characterise lyophilisers at both laboratory and commercial scale to design a focused validation strategy for commercialising parenteral drug products. Vial heat transfer coefficients (Kv) and equipment mass transfer boundaries were generated for a Lyostar II and three commercial scale IMA Lyomax lyophilisers. Kv studies were performed using gravimetric methodologies
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PLGA-based nanoparticles for the treatment of cancer: current strategies and perspectives AAPS Open Pub Date : 2022-08-01 Alvi, Maria, Yaqoob, Azka, Rehman, Kanwal, Shoaib, Syed Muhammad, Akash, Muhammad Sajid Hamid
Research on cancer treatment is always of great importance because of the extensive and difficult treatment options and side effects of chemotherapeutic agents. Due to this, novel techniques for cancer treatment are the need of the day. Nowadays, nanotechnology is of great interest for its applications as diagnostic tools, theragnostic, contrasting agents, and vehicles for delivering drugs. Nanoparticles
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Correction: Safety and pharmacokinetics of a highly bioavailable resveratrol preparation (JOTROL TM) AAPS Open Pub Date : 2022-07-27 Kemper, Christopher, Behnam, Dariush, Brothers, Shaun, Wahlestedt, Claes, Volmar, Claude-Henry, Bennett, Daniel, Hayward, Marshall
Correction: AAPS Open 8, 11 (2022) https://doi.org/10.1186/s41120-022-00058-1 Following publication of the original article (Kemper et al., 2022), the authors identified an error in the author name Dariush Behnam. The family name was incorrectly used throughout the article. The incorrect author name is: Dariush Benham The correct author name is: Dariush Behnam The sentence currently in the Introduction
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Safety and pharmacokinetics of a highly bioavailable resveratrol preparation (JOTROL TM) AAPS Open Pub Date : 2022-06-30 Kemper, Christopher, Benham, Dariush, Brothers, Shaun, Wahlestedt, Claes, Volmar, Claude-Henry, Bennett, Daniel, Hayward, Marshall
Resveratrol exhibits a wide range of biological properties, including anti-glycation, antioxidant, anti-inflammation, neuroprotective (including against advanced dementia and Alzheimer’s disease), anti-cancer, and anti-aging activity in experimental models (Galiniak et al., Acta Biochim Pol 66:13-21, 2019). Unfortunately, this compound exhibits low bioavailability and solubility (Galiniak et al., Acta
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Utilizing cross-product prior knowledge to rapidly de-risk chemical liabilities in therapeutic antibody candidates AAPS Open Pub Date : 2022-05-23 Jacobitz, Alex W., Rodezno, Wilfredo, Agrawal, Neeraj J.
There is considerable pressure in the pharmaceutical industry to advance better molecules faster. One pervasive concern for protein-based therapeutics is the presence of potential chemical liabilities. We have developed a simple methodology for rapidly de-risking specific chemical concerns in antibody-based molecules using prior knowledge of each individual liability at a specific position in the molecule’s
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Molecular docking assisted exploration on solubilization of poorly soluble drug remdesivir in sulfobutyl ether-tycyclodextrin AAPS Open Pub Date : 2022-04-25 Zhang, Yumeng, Zhao, Zhouming, Wang, Kai, Lyu, Kangjie, Yao, Cai, Li, Lin, Shen, Xia, Liu, Tengfei, Guo, Xiaodi, Li, Haiyan, Wang, Wenshou, Lai, Tsai-Ta
To study structure-specific solubilization effect of Sulfobutyl ether-β-cyclodextrin (SBE-β-CD) on Remdesivir (RDV) and to understand the experimental clathration with the aid of quantum mechanics (QM), molecular docking and molecular dynamics (MD) calculations. The experiment was carried out by phase solubility method at various pH and temperatures, while the concentration of Remdesivir in the solution
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Heat pre-treatment can abolish anti-drug antibody interference in ligand binding pharmacokinetic assays AAPS Open Pub Date : 2022-04-11 Poulsen, Svend, Jørgensen, Louise, Galle, Pia Søndergaard
Anti-drug antibodies (ADAs) can interfere with ligand binding assays (LBAs) by binding to epitopes recognized by the assay antibodies or by preventing assay antibody binding through steric hindrance. This can lead to underestimation of total drug concentration in pharmacokinetic (PK) samples which can confound decisions during drug development. We hypothesized that ADA interference in LBAs can be removed
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Pharmacokinetic and pharmacodynamic analyses of terlipressin in patients with hepatorenal syndrome AAPS Open Pub Date : 2022-04-04 Wang, Xiaofeng, Jamil, Khurram
The objective of this population pharmacokinetics (PK) analysis was to characterize the PK of terlipressin and its active metabolite, lysine-vasopressin (L-VP), in patients with hepatorenal syndrome (HRS), following intravenous administration of terlipressin 1 mg to 2 mg every 6 h. Sparse PK samples from 69 patients with HRS who participated in terlipressin phase 3 clinical studies were used for model
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Understanding the implication of Kawakita model parameters using in-die force-displacement curve analysis for compacted and non-compacted API powders AAPS Open Pub Date : 2022-03-28 Rashid, Iyad, Haddadin, Rula Raji, Alkafaween, Ashaar Abdulsalam, Alkaraki, Rawan Nayef, Alkasasbeh, Rehan Mohammad
The aim of this study was to investigate powder mechanics upon compression using data obtained from force-displacement (F-D) curves. The Kawakita model of powder compression analysis was adopted in order to compare the pressure-volume reduction relationship of the drug powders in relation to the F-D curves. Experiments were carried out on six model drugs (metronidazole, metformin, secnidazole, ciprofloxacin
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The degradation of poloxamer 188 in buffered formulation conditions AAPS Open Pub Date : 2022-03-21 Chen, Wei, Stolz, Siegfried, Wegbecher, Vincent, Parakkattel, Dixy, Haeuser, Christina, Oltra, Nuria Sancho, Kishore, Ravuri S. K., Bond, Steven, Bell, Christian, Kopf, Robert
Poloxamer 188 (P188) as a non-ionic surfactant is used in proteinaceous formulations to prevent protein adsorption to hydrophobic surfaces and unfolding at interfaces, preventing the formation of aggregates and particles. Its chemical intactness is crucial to the stability of drug products due to its protecting effects at interfaces. In order to identify and mitigate potential risks that might cause
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Therapeutic effects of dracocephalum heterophyllum in collagen-induced arthritis AAPS Open Pub Date : 2022-03-01 Wang, Yalan, Lai, Dongming, Geng, Yunyun, Shang, Peng, Wang, Pu
Rheumatoid arthritis (RA) is an autoimmune and inflammatory disease characterized by synovial inflammation, joint swelling, and cartilage and bone destruction. Dracocephalum heterophyllum (DH) is a compound in traditional Chinese herbal medicine well known for its anti-inflammatory, antiviral and antioxidant activities. In the present work, the therapeutic effects of DH were investigated in collagen-induced
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Impact of charge patches on tumor disposition and biodistribution of therapeutic antibodies AAPS Open Pub Date : 2022-02-15 Stüber, Jakob C., Rechberger, Karin F., Miladinović, Saša M., Pöschinger, Thomas, Zimmermann, Tamara, Villenave, Remi, Eigenmann, Miro J., Kraft, Thomas E., Shah, Dhaval K., Kettenberger, Hubert, Richter, Wolfgang F.
This study explores the impact of antibody surface charge on tissue distribution into various tissues including tumor. Tumor-bearing mice were dosed intravenously with a mixture comprising three antibodies engineered to carry negative charge patches, a balanced charge distribution, or positive patches, respectively (cassette dosing). Tissue levels were analyzed with a specific LC-MS/MS method. In addition
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Best practices for the development and fit-for-purpose validation of biomarker methods: a conference report AAPS Open Pub Date : 2022-02-01 Mathews, Joel, Amaravadi, Lakshmi, Eck, Steven, Stevenson, Lauren, Wang, Yow-Ming C., Devanarayan, Viswanath, Allinson, John, Lundsten, Kelly, Gunsior, Michele, Ni, Yan G., Pepin, Marc-Olivier, Gagnon, Audrey, Sheldon, Curtis, Trampont, Paul C., Litwin, Virginia
This conference report summarized a full-day workshop, “best practices for the development and fit-for-purpose validation of biomarker methods,” which was held prior to the American Association of Pharmaceutical Scientists (AAPS) PharmSci360 Congress, San Antonio, TX, November 2019. The purpose of the workshop was to bring together thought leaders in biomarker assay development in order to identify
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Development and validation of a headspace GC-MS method to evaluate the interconversion of impurities and the product quality of liquid hand sanitizers AAPS Open Pub Date : 2022-01-17 Abrigo, Nicolas, Ruzicka, Connie, Faustino, Patrick, Stiber, Neil, NguyenPho, Agnes, O’Connor, Thomas, Shakleya, Diaa
The COVID-19 pandemic has led to increased usage of hand sanitizer products by the public to prevent the spread of COVID-19 and decrease the likelihood of acquiring the disease. The increase in demand has also led to an increase in the number of manufacturers. This work describes the FDA’s Center for Drug Evaluation and Research (CDER) laboratories efforts to develop tests to assess the quality of
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Preparation of O/W nano-emulsion containing nettle and fenugreek extract and cumin essential oil for evaluating antidiabetic properties AAPS Open Pub Date : 2021-12-28 Javadi, Sara, Kazemi, Negar Motakef, Halabian, Raheleh
The oil-in-water (O/W) nano-emulsion (NE) is expanded to enhance the bioavailability of hydrophobic compounds. The NE can be prepared by herbal extract and essential oil as herbal medicines for antidiabetic treatment. In the present study, the O/W NE was prepared by fenugreek extract (FE), nettle extract (NE), and cumin essential oil (CEO) using tween 80 and span 80 surfactants in an ultrasonic bath
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An industrial case study: QbD to accelerate time-to-market of a drug product AAPS Open Pub Date : 2021-12-24 Testas, Madalena, da Cunha Sais, Tiago, Medinilha, Leonardo Piccoli, Niwa, Katia Nami Ito, de Carvalho, Lucas Sponton, Maia, Silvia Duarte, Flores, Anderson, Braz, Lígia Pedroso, Menezes, José Cardoso, Yamakawa, Cássio Yooiti
The use of a Quality by Design (QbD) approach in the development of pharmaceutical products is known to bring many advantages to the table, such as increased product and process knowledge, robust manufacturing processes, and regulatory flexibility regarding changes during the commercial phase. However, many companies still adhere to a more traditional pharmaceutical process development—in some cases
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A bridging assay for detection and characterization of anti-drug antibodies to dostarlimab, a new anti-PD-1 therapeutic monoclonal antibody AAPS Open Pub Date : 2021-12-20 Patterson, Marilyn, Beausang, Lee Anne, Rup, Bonita, Bowsher, Ronald R., Krug, Kim, Melhem, Murad, Lu, Sharon
Dostarlimab (JEMPERLI) is a humanized anti-programmed death 1 (PD-1) immunoglobulin (Ig)G4-kappa monoclonal antibody that binds to the PD-1 receptor and competitively inhibits binding of its ligands, PD-L1 and PD-L2. Dostarlimab was recently approved in the USA and the European Union. Because dostarlimab is a macromolecular therapeutic, it has the potential to elicit the formation of anti-drug antibodies
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A risk-based approach to validation of ion chromatography methods using suppressed conductivity AAPS Open Pub Date : 2021-12-13 Nelson, Deanna J., Marbury, G. Dean
Ion chromatography (IC) has evolved into one of the most widely used separation techniques of analytical chemistry. Consequently, the number of users of this method is continuously growing. Analysts often assume that widely used guidelines for HPLC method validation in regulated environments routinely apply to IC. This manuscript provides an analysis of the potential shortcomings of traditional approaches
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Gamma oryzanol niosomal gel for skin cancer: formulation and optimization using quality by design (QbD) approach AAPS Open Pub Date : 2021-12-06 Shah, Harsh S., Gotecha, Ankit, Jetha, Dolly, Rajput, Amarjitsing, Bariya, Aditi, Panchal, Shital, Butani, Shital
Skin cancer is fifth most diagnosed disease in human population due to ultraviolet radiation (UV) exposure. Gamma oryzanol (OZ) is a natural antioxidant, and it also has skin anti-aging properties. OZ is naturally found in rice bran oil. The main aim of the present work was to optimize OZ niosomal formulation using quality by design approach including one variable at a time and full factorial design
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Meeting Report: Vaccine Stability Considerations to Enable Rapid Development and Deployment AAPS Open Pub Date : 2021-12-01 Alasandro, Mark, Choudhury, Dilip, Huynh-Ba, Kim, Kochling, Jianmei, Latoz, Christopher, Larkin, Laure, McCaig, Lori, Subbarao, Nanda, Wu, Yan, Zhang, Yajie
The Stability Community of the American Association of Pharmaceutical Scientists (AAPS) held a virtual workshop on “Vaccine Stability Considerations to Enable Rapid Development and Deployment”, on March 24-25, 2021. The workshop included distinguished speakers and panelists from across the industry, academia, regulatory agencies, as well as health care leaders. This paper presents a review of the topics
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Designing an ideal alcohol-based hand sanitizer: in vitro antibacterial responses of ethanol and isopropyl alcohol solutions to changing composition AAPS Open Pub Date : 2021-11-22 Nzekwe, Ifeanyi T., Agwuka, Onyedika I., Okezie, Moses U., Fasheun, Daniel O., Nnamani, Petra O., Agubata, Chukwuma O.
This study aimed to achieve an in vitro quantification of the effects of composition and formulation factors on the killing rates of alcohol-based hand sanitizers. The killing rates of 85% ethyl alcohol (ET) and isopropyl alcohol (IPA) were studied under different conditions such as pH, electrolyte concentration, or inclusion of herbal extracts (cucumber, carrot, and aloe vera), a quaternary ammonium
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AAPS open social media strategy (2021–2025) AAPS Open Pub Date : 2021-11-15 Shah, Harsh S.
Social media has become an important and effective tool for researchers for direct dissemination of their research findings to a larger audience. AAPS Open recognized this trend and strategically decided to offer an ideal platform to the researchers to raise their profile via AAPS Open’s social media support. With my commitment towards supporting outreach activities in pharmaceutical field, I gracefully
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A competitive ligand-binding assay for the detection of neutralizing antibodies against dostarlimab (TSR-042) AAPS Open Pub Date : 2021-11-11 Zhang, Xiaolong Tom, Chen, Hong, Shao, Weiping, Lin, Zhongping John, Melhem, Murad, Lu, Sharon
Dostarlimab is a humanized anti–PD-1 monoclonal antibody. Dostarlimab (JEMPERLI; TSR-042) was recently approved in the USA and in the EU. The presence of neutralizing antibodies (NAbs) is a cause for concern because they block the therapeutic function of the antibody and reduce drug efficacy. Therefore, programs developing therapeutic biologics need to develop and validate assays that adequately assess
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Tritium labeling of antisense oligonucleotides via different conjugation agents AAPS Open Pub Date : 2021-11-15 Edelmann, Martin R., Husser, Christophe, Duschmalé, Martina B., Fischer, Guy, Senn, Claudia, Koller, Erich, Brink, Andreas
A novel approach to tritium-labeled antisense oligonucleotides (ASO) was established by conjugating N-succinimidyl propionate, as well as maleimide-derivatives, to the 3′-end of ASOs targeting metastasis-associated lung adenocarcinoma transcript 1 (Malat1) containing amino- or sulfhydryl-linkers. In vitro stability and Malat1 RNA reduction studies demonstrated that N-ethylmaleimide (NEM) could be used
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Perspectives in modeling and model validation during analytical quality by design chromatographic method evaluation: a case study AAPS Open Pub Date : 2021-09-01 Dong, Yongzhi, Liu, Zhimin, Li, Charles, Pinter, Emily, Potts, Alan, Tadey, Tanya, Weiser, William
Design of experiments (DOE)-based analytical quality by design (AQbD) method evaluation, development, and validation is gaining momentum and has the potential to create robust chromatographic methods through deeper understanding and control of variability. In this paper, a case study is used to explore the pros, cons, and pitfalls of using various chromatographic responses as modeling targets during
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Pharmacokinetics and biodistribution of a novel anticancer thyrointegrin αvβ3 antagonist: triazole modified tetraiodothyroacetic acid conjugated to polyethylene glycol (P-bi-TAT) AAPS Open Pub Date : 2021-08-16 Fujioka, Kazutoshi, Godugu, Kavitha, Mousa, Shaker A.
We previously developed a triazole modified tetraiodothyroacetic acid (TAT) conjugated to a polyethylene glycol (PEG)-based thyrointegrin αvβ3 antagonist targeted compound, called P-bi-TAT. It exhibited potent anti-angiogenic and anticancer activities in vivo. The objective of the current study is to develop a quantitative bioanalytical method for P-bi-TAT using liquid chromatography-tandem mass spectrometry
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Dawn of a new beginning AAPS Open Pub Date : 2021-06-11 Andrea Allmendinger
Welcome Pharmaceutical Scientist community! This is my first editorial and I would like to take the opportunity to sincerely thank AAPS and Springer Nature for their trust, recognition, and support in stepping into this leadership role — a responsible and challenging task! I am excited to connect to the scientific community creating an open access space for pharmaceutical sciences. I would like to
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Utilization of risk-based predictive stability within regulatory submissions; industry’s experience AAPS Open Pub Date : 2020-05-11 Megan McMahon, Helen Williams, Elke Debie, Mingkun Fu, Robert Bujalski, Fenghe Qiu, Yan Wu, Hanlin Li, Jin Wang, Cherokee Hoaglund-Hyzer, Donnie Pulliam
Risk-Based Predictive Stability (RBPS) tools, such as the Accelerated Stability Assessment Program (ASAP) and other models, are used routinely within pharmaceutical development to quickly assess stability characteristics, especially to understand mechanisms of degradation. These modeling tools provide stability insights within weeks that could take months or years to understand using long-term stability
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Similarity assessment of quality attributes of biological medicines: the calculation of operating characteristics to compare different statistical approaches AAPS Open Pub Date : 2019-09-10 Thomas Stangler, Martin Schiestl
The comparison of quality attributes is a key element in the evaluation of both biosimilars and manufacturing process changes for biological medicines. Different statistical approaches are proposed to facilitate such evaluations. However, there is no regulatory consensus on a quantitative and scientifically justified definition and an underlying hypothesis of a statistically equivalent quality. The
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Drug manufacturing and access to medicines: the West African story. A literature review of challenges and proposed remediation AAPS Open Pub Date : 2019-08-05 Abigail A. Ekeigwe
It is the right of all humans to have access to safe, quality and effective medicines. This article seeks to expound on the problems of drug manufacturing and challenges of accessing medicines in West Africa, and evaluate the strategies being adopted by international developmental partners and the governments to address them. West Africa is uniquely diverse in culture (having English, French and Portuguese
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Substandard and falsified medicine screening technologies AAPS Open Pub Date : 2019-07-08 Lukas Roth, Kevin B. Biggs, Daniel K. Bempong
Substandard and falsified medicine screening technologies are invaluable tools for post-marketing surveillance of medicine quality, particularly in low- and middle-income countries. National Regulatory Authorities and their partners leverage screening technologies to detect substandard and falsified medicines in the field and eliminate them from the medical product supply chain. An arsenal of different
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Development and evaluation of taste masked dry syrup formulation of potassium chloride. AAPS Open Pub Date : 2019-01-22 Madhur Kulkarni,Brijesh Vishwakarma,Samik Sen,Sandhya Anupuram,Abhijit A Date
Potassium chloride (KCl) syrup is widely used for the oral treatment of the hypokalemia. However, it is associated with unacceptable taste. In the present study, we sought to develop a palatable and easy to reconstitute KCl dry syrup as a commercially viable alternative to currently available KCl syrup. We explored the potential of Eudragit E100 as a taste-masking polymer to coat and improve the palatability
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ANVISA: an introduction to a new regulatory agency with many challenges AAPS Open Pub Date : 2018-12-12 Kim Huynh-Ba, Alexandra Beumer Sassi
Brazil, the largest country in South America, has become the second largest pharmaceutical market in the emerging world. The Brazillian Health Surveillance Agency (Agencia Nacional de Vigilancia Sanitaria - ANVISA) was created in 1999 with the primary goal to protect and promote public health surveillance over products and services in Brazil. The governing body and structure of this new regulatory