By Aliasger K. Salem, Ph.D.
The AAPS Journal, an official journal of the American Association of Pharmaceutical Scientists, has been publishing in-depth papers in the broad area of pharmaceutical sciences. These papers included analytical studies, machine learning, formulation and dissolution studies, drug delivery studies and pharmacokinetic studies amongst others and included the completion of a theme issue on “Rising Stars in Drug Delivery and Novel Carriers” [1]. The theme issue included a review on nanotechnology-driven cell-based therapies in regenerative medicine and a research article on zwitterionic polymer coatings that enhance gold nanoparticle stability and uptake in various biological environments [2, 3]. In other drug delivery related articles, Ainslie and colleagues reported on nano/microparticle formulations for universal influenza vaccines [4] and Balthasar and colleagues reported on the targeted delivery of endosomal escape peptides to enhance immunotoxin potency and anti-cancer efficacy [5]. In 2023, we published a special theme issue on “Recent Advances in Drug Delivery”.
A major focus of The AAPS Journal continues to be research in monoclonal antibodies and anti-drug antibodies. In the area of monoclonal antibodies, Hu et al discussed monoclonal antibody PK prediction models in Cynomolgus monkeys following SC administration [6]. Rathore reported on a model based control of single-pass tangential flow ultrafiltration in process analytical technology implementation for membrane operations in continuous manufacturing of molecular antibodies [7]. Partridge and colleagues reported on the interference in a neutralizing antibody assay for Odronextamab, a CD20xCD3 Bispecific molecular antibody, from prior Rituximab therapy and presented a possible mitigation strategy [8].
With respect to anti-drug antibodies, Stubenrauch and colleagues discussed pre-clinical observation of systemic and ocular anti-drug antibody responses to intravitreally administered drugs [9]. Helmy and colleagues showed that neutralization activity of anti-drug antibodies against biotherapeutics can be predicted from PK/PD and anti-drug antibody data [10]. Devanarayan and colleagues carried out a comparison of titer and signal to noise for determination of anti-drug antibody magnitude using clinical data [11]. Sumner reported on the characterization and mitigation of interference in a bridging anti-drug antibody assay [12]. The European Immunogenicity Platform presented an opinion on when to extend monitoring of anti-drug antibodies for high-risk biotherapeutics in clinical trials [13]. Bruno and colleagues reported on the tumor growth inhibition-overall survival model for subgroup analysis based on post-randomization factors with a focus on the application for anti-drug antibody (ADA) subgroup analysis of Atezolizumab [14]. Lepsy and colleagues showed that determination of anti-drug antibody affinity in clinical study samples provides a tool for evaluation of immune response maturation[15]. Jani et al reported on anti-drug antibody sample testing and reporting harmonization [16].
An additional area represented in the AAPS Journal in 2022 was antibody-drug conjugates. Meng and colleagues reported on the joint disposition properties and comprehensive pharmacokinetic characterization of antibody-drug conjugates [17]. Chen and colleagues carried out a case study on selection of payloads for antibody-drug conjugates targeting ubiquitously expressed tumor-associated antigens [18]. Thurber and colleagues showed the PK/PD of TAK-164 antibody-drug conjugates coadministered with unconjugated antibody [19].
The AAPS Journal has consistently been a destination for PK/PD and modelling studies and that continued to be the case in 2022. Vermeulen and colleagues presented a review on the PK of long-acting formulations in different species [20]. Martinez and colleagues presented reflections on individualized patient care through model-informed precision dosing [21]. Frances and colleagues integrated preclinical in vivo data into a modelling network to inform a clinical strategy for a CD3 T-cell Bispecific in combination with anti-PD-L1 [22]. Gieseker and colleagues provided an update on a database for PK and drug residue literature in fish [23]. Ovacik and colleagues presented non-clinical PK/PD data from a BCMA/CD16A antibody used for treatment of multiple myeloma [24]. Zhao and colleagues compared a bayesian approach with two one-sided T-tests for bioequivalence studies [25]. Jeong and Jusko assessed the limiting conditions for determinants of biological half-lives and terminal slopes in physiologically based PK systems [26]. Chung and colleagues presented the practical application of tissue lumping theories for PK of various compounds and the theoretical consideration of bottom-up approach of lumping tissues in whole-body PBPK for the determination of the number of tissue groups of kinetically distinct transit time in whole-body PBPK models [27, 28]. Willman and colleagues discussed the challenges of applying PK/PD principles to Nifurtimox dose finding for treatment of chagas disease in pediatric patients [29]. The IQ Human PK Prediction Working Group presented findings on current approaches for predicting human PK for small molecule development candidates [30]. Jackson and Foehl carried out a simulation study of the comparative performance of partial area under the curve and partial area under the effect curve metrics in crossover versus replicated crossover bioequivalence studies for concerta and Ritalin LA [31]. Wang and colleagues reported on a model-informed approach supporting approval of Adalimumab (HUMIRA) in pediatric patients with ulcerative colitis from a regulatory perspective [32]. Rostami-Hodjegan and colleagues presented a proof of concept in assignment of within-subject variability during virtual bioequivalence studies with a focus on propagation of intra-subject variation in gastrointestinal physiology using physiologically based PK modeling [33]. Metsvaht and colleagues reported on the PK of Gentamicin components C1, C1a, and C2/C2a/C2b and subsequent decline in glomerular filtration rate in neonates [34]. Gill and Jones discussed the opportunities and challenges for PBPK model of molecular antibodies in pediatrics and pregnancy [35]. Hu presented a general biphasic bodyweight model for scaling basal metabolic rate, glomerular filtration rate, and drug clearance from birth to adulthood [36]. Shah and colleagues reported on the effect of the size of protein therapeutics on brain PK following systematic administration [37]. Zhao and colleagues presented on the application of modeling and simulation to identify a shortened study duration and novel bioequivalence metric for a long-acting intrauterine system [38]. Peng and colleagues described a fit-for-purpose method to measure circulating levels of the mRNA component of a liposomal-formulated individualized neoantigen-specific therapy for cancer [39]. Woolf and colleagues reported on an investigation of instability in dried blood spot samples for PK sampling in Phase 3 trials of Verubecestat [40]. Dockendorf et al complemented this report with a model-based approach to bridging plasma and dried blood spot concentration data for Phase 3 Verubecestat trials [41]. Jansson-Löfmark and colleagues reported on the population PD modeling of Eflornithine-based treatments against late-stage Gambiense Human African Trypanosomiasis and efficacy predictions of L-eflornithine-based therapy [42]. Fandozzi and colleagues carried out an in vitro assessment of transporter mediated perpetrator DDIs for several Hepatitis C virus direct-acting antiviral drugs and prediction of DDIs with statins using static models [43]. Shah and Hong presented a model for long acting injectables based on PK and Physical Chemical Properties [44]. Marroum and colleagues showed the utility of modeling and simulation approach to support the clinical relevance of dissolution specifications using a case study from Upadacitinib development [45]. Xia and colleagues presented their perspective of DMPK on recombinant adeno-associated virus-based gene therapy [46]. Ogungbenro and colleagues reported on in vitro to in vivo extrapolation linked to physiologically based PK models for assessing the brain drug disposition [47]. Fotaki and colleagues reported on the performance evaluation of Montelukast pediatric formulations with a focus on age-related in vitro conditions and PBPK modelling approaches [48, 49].
An interesting parameter evaluated in a number of published studies in The AAPS Journal in 2022 was food. Zou reviewed the effects of food on PK of non-orally delivered drugs [50]. Emami Riedmaier discussed progress on predicting food effects [51]. Complimenting this work, Martinez provided a critical overview of the biological effects of excipients with a focus on the impact on gastrointestinal absorption and scientific considerations and tools for oral product development [52, 53].
Dissolution research was strongly represented in the AAPS Journal in 2022. Cohen and colleagues discussed challenges and strategies for solubility and dissolution methods for amorphous solid dispersions [54]. Polli discussed a simple equation for accommodating sink versus non-sink conditions via drug solubility and dissolution volume [55]. Amidon and colleagues presented dissolution challenges associated with the surface pH of drug particles and utilized mechanistic oral absorption modeling [56]. Abend and colleagues discussed dissolution profile similarity analyses [57]. Sharp-Suarez and colleagues reported on current approaches for dissolution similarity assessment, requirements, and global expectations [58]. An IQ Consortium presented a perspective on connecting dissolution methods to in vivo performance [59]. Gao and colleagues reviewed the development of in vitro dissolution testing methods to simulate fed conditions for immediate release solid oral dosage forms [60]. Benet and colleagues provide an update on the biopharmaceutics drug disposition classification system (BDDCS) [61]. Metry and Polli presented an evaluation of excipient risk in BCS class I and III biowaivers [62]. Seo and colleagues reported on the application of solubility and dissolution profile comparison for prediction of gastric pH-mediated drug-drug interactions [63]. Kourentas and colleagues simulated the intraluminal performance of lipophilic weak bases in fasted healthy adults using DDDPlusTM [64].
Another area strongly represented in the AAPS Journal in 2022 that is complimentary with dissolution studies is formulation and manufacturing. Viehmann and colleagues presented benchmarks for quality practices of global manufacturing [65]. Anderson and colleagues carried out a comparison between pure component modeling approaches for monitoring pharmaceutical powder blends with near-infrared spectroscopy in continuous manufacturing schemes [66]. Singh et al discussed an end-to-end approach to surfactant selection, risk mitigation and control strategies for protein-based therapeutics [67]. Sinkó and colleagues presented a proof-of-concept study on flux-based formulation development [68]. Mohanty and colleagues reported on the preservation of mRNA at elevated temperatures in capillary-mediated vitrification [69]. Vick and colleagues discussed biological matrix supply chain shortages [70].
Analytical assay development and biomarkers continued to have a strong presence in the AAPS Journal in 2022. Loughney and colleagues described high throughput methodology for overcoming biopharmaceutical interferents in quantifying host cell DNA [71]. Zahel presented a novel bootstrapping test for analytical biosimilarity [72]. Yeung and colleagues presented an anion-exchange chromatography analysis method for adeno-associated virus empty capsid content [73]. Mao et al described the development of a near-infrared spectroscopy method to characterize powder blend heterogeneity in direct compression formulations [74]. Di et al evaluated accuracy of plasma protein binding measurements using a dilution method [75]. Deng and colleagues reported on the stability and function of extracellular vesicles from corneal stem cells [76]. Morris and colleagues identified potential megalin/cubilin substrates using proteomic quantification from megalin knockdown mice [77]. Drennan and colleagues discussed NIR spectroscopy as an online PAT tool for narrow therapeutic index drugs [78]. Wang and Takiar presented scientific considerations for stability studies of drug substances supporting abbreviated new drug applications [79]. Allen and colleagues discussed considerations in the immunogenicity assessment strategy for oligonucleotide therapeutics [80]. Siegel and colleagues used caffeine to test an artificial gut simulator [81]. Steenwyk and colleagues presented biomarker assay validation by mass spectrometry [82]. Hays et al asked the question on whether incurred sample reanalysis is applicable in biomarker assays [83]. Völler and colleagues reported on the prediction of glomerular filtration rate maturation across preterm and term neonates and young infants using inulin as a marker [84]. Williams and colleagues reported on the best practices in qPCR and dPCR validation in regulated bioanalytical laboratories [85]. Ranheim and colleagues reported on analytical quality by design, life cycle management, and method control [86].
The formation of nitrosamines in medicines has emerged as an important issue in the last few years. Wierer and colleagues reported on an international regulatory collaboration on the analysis of nitrosamines in Metformin-containing medicines [87]. This was complimented by work from Mowery and colleagues, who reported on a full evaporation static headspace gas chromatography method with nitrogen phosphorous detection for ultrasensitive analysis of semi-volatile nitrosamines in pharmaceutical products [88].
Machine learning and artificial intelligence is an area of growing interest in the pharmaceutical sciences. In 2022, Zhang and colleagues reviewed machine learning and artificial intelligence in pharmaceutical research and development [89]. Nagy and colleagues reviewed the application of artificial neural networks in the process analytical technology of pharmaceutical manufacturing [90]. Zou and colleagues discussed machine learning prediction of clinical trial operational efficiency [91]. Zhang and colleagues reported on semisolid pharmaceutical product characterization using non-invasive X-ray microscopy and AI-based image analytics [92].
COVID-19 and Monkey Pox were both ongoing health concerns in 2022. Mrsny discussed intradermal vaccinations for monkeypox [93]. Osborne and colleagues provided reflections on chemistry manufacturing and controls development for pandemic therapies and vaccines [94]. Zhao et al discussed use of compartmental models in predicting COVID-19 outbreaks [95]. Hoeng and colleagues reported on in vitro experimentation to human dosing predictions for pulmonary delivery of aerosolized chloroquine and hydroxychloroquine to treat COVID-19 [96].
Other areas of pharmaceutical sciences were also covered in the AAPS Journal in 2022. For example, Salimi-Moosavi and Soto presented a non-radiometric approach to determine tissue vascular blood volume in biodistribution studies[97]. Kong and colleagues discussed a model for DNA methylone and transcriptome studies of Triterpenoid CDDO in TPA-mediated skin carcinogenesis [98]. LeBarre and colleagues discussed risk, expression and immunogenicity of recombinant human hyaluronidase PH20 enzymes [99]. Roche and colleagues showed FOLFIRINOX PD interactions in 2D and 3D pancreatic cancer cells [100]. Chothe and colleagues evaluated the role of sinusoidal organic anion-transporting polypeptide 1B1/1B3 and bile canalicular multidrug resistance-associated protein 2 on a STING agonist [101]. Sharma and colleagues reported on the metabolism of speciociliatine [102]. Pang and colleagues reported on the significance of the Vitamin D receptor on crosstalk with nuclear receptors and regulation of enzymes and transporters [103]. Petersson and colleagues reported on multi-well array culture of primary human hepatocyte spheroids for clearance extrapolation of slowly metabolized compounds [104]. Kong and colleagues reported on how Nfe2l2 regulates metabolic rewiring and epigenetic reprogramming in mediating cancer protective effect by Fucoxanthin [105].
In summary, 2022-2023 was a great year for the AAPS Journal with topics in analytical methods, PK/PD and modelling, dissolution, machine learning, drug delivery and formulation development amongst others all strongly represented. The journal looks forward to continuing to publish strong high-quality manuscripts in these areas.
References
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2. Alzate-Correa, D., et al., Nanotechnology-Driven Cell-Based Therapies in Regenerative Medicine. AAPS J, 2022. 24(2): p. 43.
3. King, B.M. and J. Fiegel, Zwitterionic Polymer Coatings Enhance Gold Nanoparticle Stability and Uptake in Various Biological Environments. AAPS J, 2022. 24(1): p. 18.
4. Hendy, D.A., et al., Nano/microparticle Formulations for Universal Influenza Vaccines. AAPS J, 2022. 24(1): p. 24.
5. Polli, J.R., et al., Targeted Delivery of Endosomal Escape Peptides to Enhance Immunotoxin Potency and Anti-cancer Efficacy. AAPS J, 2022. 24(3): p. 47.
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17. Liao, K.H., et al., Joint Disposition Properties and Comprehensive Pharmacokinetic Characterization of Antibody-Drug Conjugates. AAPS J, 2022. 24(4): p. 73.
18. Yao, B., et al., Selection of Payloads for Antibody-Drug Conjugates Targeting Ubiquitously Expressed Tumor-Associated Antigens: a Case Study. AAPS J, 2022. 24(4): p. 70.
19. Menezes, B., et al., Pharmacokinetics and Pharmacodynamics of TAK-164 Antibody Drug Conjugate Coadministered with Unconjugated Antibody. AAPS J, 2022. 24(6): p. 107.
20. Nguyen, V.T.T., N. Darville, and A. Vermeulen, Pharmacokinetics of Long-Acting Aqueous Nano-/Microsuspensions After Intramuscular Administration in Different Animal Species and Humans-a Review. AAPS J, 2022. 25(1): p. 4.
21. Jelliffe, R., et al., Individualized Patient Care Through Model-Informed Precision Dosing: Reflections on Training Future Practitioners. AAPS J, 2022. 24(6): p. 117.
22. Sanchez, J., et al., Preclinical InVivo Data Integrated in a Modeling Network Informs a Refined Clinical Strategy for a CD3 T-Cell Bispecific in Combination with Anti-PD-L1. AAPS J, 2022. 24(6): p. 106.
23. Crosby, T.C., E.C. Kittel, and C.M. Gieseker, Phish-Pharm: A Searchable Database of Pharmacokinetics and Drug Residue Literature in Fish - 2022 Update. AAPS J, 2022. 24(6): p. 105.
24. Cai, H., et al., Nonclinical Pharmacokinetics, Pharmacodynamics, and Translational Model of RO7297089, A Novel Anti-BCMA/CD16A Bispecific Tetravalent Antibody for the Treatment of Multiple Myeloma. AAPS J, 2022. 24(6): p. 100.
25. Peck, C., et al., Comparing a Bayesian Approach (BEST) with the Two One-Sided t-Tests (TOSTs) for Bioequivalence Studies. AAPS J, 2022. 24(5): p. 97.
26. Jeong, Y.S. and W.J. Jusko, Determinants of Biological Half-Lives and Terminal Slopes in Physiologically Based Pharmacokinetic Systems: Assessment of Limiting Conditions. AAPS J, 2022. 24(5): p. 96.
27. Jeong, Y.S., M.S. Kim, and S.J. Chung, Determination of the Number of Tissue Groups of Kinetically Distinct Transit Time in Whole-Body Physiologically Based Pharmacokinetic (PBPK) Models II: Practical Application of Tissue Lumping Theories for Pharmacokinetics of Various Compounds. AAPS J, 2022. 24(5): p. 91.
28. Jeong, Y.S., M.S. Kim, and S.J. Chung, Determination of the Number of Tissue Groups of Kinetically Distinct Transit Time in Whole-Body Physiologically Based Pharmacokinetic (PBPK) Models I: Theoretical Consideration of Bottom-Up Approach of Lumping Tissues in Whole-Body PBPK. AAPS J, 2022. 24(5): p. 90.
29. Stass, H., et al., Nifurtimox for Treatment of Chagas Disease in Pediatric Patients: the Challenges of Applying Pharmacokinetic-Pharmacodynamic Principles to Dose Finding. AAPS J, 2022. 24(5): p. 92.
30. Petersson, C., et al., Current Approaches for Predicting Human PK for Small Molecule Development Candidates: Findings from the IQ Human PK Prediction Working Group Survey. AAPS J, 2022. 24(5): p. 85.
31. Jackson, A.J. and H.C. Foehl, A Simulation Study of the Comparative Performance of Partial Area under the Curve (pAUC) and Partial Area under the Effect Curve (pAUEC) Metrics in Crossover Versus Replicated Crossover Bioequivalence Studies for Concerta and Ritalin LA. AAPS J, 2022. 24(4): p. 80.
32. Li, R.J., et al., Model-Informed Approach Supporting Approval of Adalimumab (HUMIRA) in Pediatric Patients with Ulcerative Colitis from a Regulatory Perspective. AAPS J, 2022. 24(4): p. 79.
33. Bego, M., et al., Proof of Concept in Assignment of Within-Subject Variability During Virtual Bioequivalence Studies: Propagation of Intra-Subject Variation in Gastrointestinal Physiology Using Physiologically Based Pharmacokinetic Modeling. AAPS J, 2022. 24(1): p. 21.
34. Soeorg, H., et al., Pharmacokinetics of Gentamicin Components C1, C1a, and C2/C2a/C2b and Subsequent Decline in Glomerular Filtration Rate in Neonates. AAPS J, 2022. 24(4): p. 77.
35. Gill, K.L. and H.M. Jones, Opportunities and Challenges for PBPK Model of mAbs in Paediatrics and Pregnancy. AAPS J, 2022. 24(4): p. 72.
36. Hu, T.M., A General Biphasic Bodyweight Model for Scaling Basal Metabolic Rate, Glomerular Filtration Rate, and Drug Clearance from Birth to Adulthood. AAPS J, 2022. 24(3): p. 67.
37. Chang, H.Y., et al., Effect of the Size of Protein Therapeutics on Brain Pharmacokinetics Following Systematic Administration. AAPS J, 2022. 24(3): p. 62.
38. Sharan, S., et al., Application of Modeling and Simulation to Identify a Shortened Study Duration and Novel Bioequivalence Metric for a Long-Acting Intrauterine System. AAPS J, 2022. 24(3): p. 63.
39. Guelman, S., et al., A Fit-for-Purpose Method to Measure Circulating Levels of the mRNA Component of a Liposomal-Formulated Individualized Neoantigen-Specific Therapy for Cancer. AAPS J, 2022. 24(3): p. 64.
40. Anderson, M., et al., An Investigation of Instability in Dried Blood Spot Samples for Pharmacokinetic Sampling in Phase 3 Trials of Verubecestat. AAPS J, 2022. 24(3): p. 52.
41. Dockendorf, M.F., et al., A Model-Based Approach to Bridging Plasma and Dried Blood Spot Concentration Data for Phase 3 Verubecestat Trials. AAPS J, 2022. 24(3): p. 53.
42. Amilon, C., et al., Population Pharmacodynamic Modeling of Eflornithine-Based Treatments Against Late-Stage Gambiense Human African Trypanosomiasis and Efficacy Predictions of L-eflornithine-Based Therapy. AAPS J, 2022. 24(3): p. 48.
43. Chu, X., et al., In Vitro Assessment of Transporter Mediated Perpetrator DDIs for Several Hepatitis C Virus Direct-Acting Antiviral Drugs and Prediction of DDIs with Statins Using Static Models. AAPS J, 2022. 24(3): p. 45.
44. Shah, J.C. and J. Hong, Model for Long Acting Injectables (Depot Formulation) Based on Pharmacokinetics and Physical Chemical Properties. AAPS J, 2022. 24(3): p. 44.
45. Mohamed, M.F., et al., Utility of Modeling and Simulation Approach to Support the Clinical Relevance of Dissolution Specifications: a Case Study from Upadacitinib Development. AAPS J, 2022. 24(2): p. 39.
46. Chen, N., et al., The Perspective of DMPK on Recombinant Adeno-Associated Virus-Based Gene Therapy: Past Learning, Current Support, and Future Contribution. AAPS J, 2022. 24(1): p. 31.
47. Murata, Y., et al., In Vitro to In Vivo Extrapolation Linked to Physiologically Based Pharmacokinetic Models for Assessing the Brain Drug Disposition. AAPS J, 2022. 24(1): p. 28.
48. Guimaraes, M., et al., Performance Evaluation of Montelukast Pediatric Formulations: Part I-Age-Related In Vitro Conditions. AAPS J, 2022. 24(1): p. 26.
49. Guimaraes, M., M. Vertzoni, and N. Fotaki, Performance Evaluation of Montelukast Pediatric Formulations: Part II - a PBPK Modelling Approach. AAPS J, 2022. 24(1): p. 27.
50. Zou, P., Does Food Affect the Pharmacokinetics of Non-orally Delivered Drugs? A Review of Currently Available Evidence. AAPS J, 2022. 24(3): p. 59.
51. Emami Riedmaier, A., Predicting Food Effects: Are We There Yet? AAPS J, 2022. 24(1): p. 25.
52. Martinez, M.N., et al., A Critical Overview of the Biological Effects of Excipients (Part I): Impact on Gastrointestinal Absorption. AAPS J, 2022. 24(3): p. 60.
53. Martinez, M.N., et al., A Critical Overview of the Biological Effects of Excipients (Part II): Scientific Considerations and Tools for Oral Product Development. AAPS J, 2022. 24(3): p. 61.
54. Hermans, A., et al., Challenges and Strategies for Solubility Measurements and Dissolution Method Development for Amorphous Solid Dispersion Formulations. AAPS J, 2022. 25(1): p. 11.
55. Polli, J.E., A Simple One-Parameter Percent Dissolved Versus Time Dissolution Equation that Accommodates Sink and Non-sink Conditions via Drug Solubility and Dissolution Volume. AAPS J, 2022. 25(1): p. 1.
56. Hens, B., et al., Dissolution Challenges Associated with the Surface pH of Drug Particles: Integration into Mechanistic Oral Absorption Modeling. AAPS J, 2022. 24(1): p. 17.
57. Hoffelder, T., et al., Dissolution Profile Similarity Analyses-Statistical Principles, Methods and Considerations. AAPS J, 2022. 24(3): p. 54.
58. Abend, A.M., et al., Current Approaches for Dissolution Similarity Assessment, Requirements, and Global Expectations. AAPS J, 2022. 24(3): p. 50.
59. Aburub, A., et al., An IQ Consortium Perspective on Connecting Dissolution Methods to In Vivo Performance: Analysis of an Industrial Database and Case Studies to Propose a Workflow. AAPS J, 2022. 24(3): p. 49.
60. Lex, T.R., et al., Development of In Vitro Dissolution Testing Methods to Simulate Fed Conditions for Immediate Release Solid Oral Dosage Forms. AAPS J, 2022. 24(2): p. 40.
61. Bocci, G., T.I. Oprea, and L.Z. Benet, State of the Art and Uses for the Biopharmaceutics Drug Disposition Classification System (BDDCS): New Additions, Revisions, and Citation References. AAPS J, 2022. 24(2): p. 37.
62. Metry, M. and J.E. Polli, Evaluation of Excipient Risk in BCS Class I and III Biowaivers. AAPS J, 2022. 24(1): p. 20.
63. Miao, L., et al., Application of Solubility and Dissolution Profile Comparison for Prediction of Gastric pH-Mediated Drug-Drug Interactions. AAPS J, 2022. 24(1): p. 35.
64. Statelova, M., M. Vertzoni, and A. Kourentas, Simulation of Intraluminal Performance of Lipophilic Weak Bases in Fasted Healthy Adults Using DDDPlus(TM). AAPS J, 2022. 24(5): p. 89.
65. Fellows, M., et al., Benchmarking the Quality Practices of Global Pharmaceutical Manufacturing to Advance Supply Chain Resilience. AAPS J, 2022. 24(6): p. 111.
66. Rish, A.J., et al., Comparison Between Pure Component Modeling Approaches for Monitoring Pharmaceutical Powder Blends with Near-Infrared Spectroscopy in Continuous Manufacturing Schemes. AAPS J, 2022. 24(4): p. 82.
67. Sreedhara, A., et al., End-to-End Approach to Surfactant Selection, Risk Mitigation, and Control Strategies for Protein-Based Therapeutics. AAPS J, 2022. 25(1): p. 6.
68. Kadar, S., et al., Flux-Based Formulation Development-A Proof of Concept Study. AAPS J, 2022. 24(1): p. 22.
69. Renu, S., et al., Capillary-Mediated Vitrification: Preservation of mRNA at Elevated Temperatures. AAPS J, 2022. 24(4): p. 75.
70. Dubiel, E.A., et al., Biological Matrix Supply Chain Shortages: More Matrices Are Now Rare-the Case for Surrogate Matrices. AAPS J, 2022. 24(2): p. 42.
71. Lauro, M.L., et al., Overcoming Biopharmaceutical Interferents for Quantitation of Host Cell DNA Using an Automated, High-Throughput Methodology. AAPS J, 2022. 25(1): p. 10.
72. Zahel, T., A Novel Bootstrapping Test for Analytical Biosimilarity. AAPS J, 2022. 24(6): p. 112.
73. Frenkel, R., et al., ACUVRA: Anion-Exchange Chromatography UV-Ratio Analysis-A QC-Friendly Method for Monitoring Adeno-Associated Virus Empty Capsid Content To Support Process Development and GMP Release Testing. AAPS J, 2022. 25(1): p. 3.
74. Shi, Z., et al., Development of a Near-Infrared Spectroscopy (NIRS)-Based Characterization Approach for Inherent Powder Blend Heterogeneity in Direct Compression Formulations. AAPS J, 2022. 25(1): p. 9.
75. Ryu, S., D. Tess, and L. Di, Addressing the Accuracy of Plasma Protein Binding Measurement for Highly Bound Compounds Using the Dilution Method. AAPS J, 2022. 25(1): p. 7.
76. Lyu, N., et al., Stability and Function of Extracellular Vesicles Derived from Immortalized Human Corneal Stromal Stem Cells: A Proof of Concept Study. AAPS J, 2022. 25(1): p. 8.
77. Zhao, B., et al., Identification of Potential Megalin/Cubilin Substrates Using Extensive Proteomics Quantification from Kidney Megalin-Knockdown Mice. AAPS J, 2022. 24(6): p. 109.
78. Talwar, S., et al., NIR Spectroscopy as an Online PAT Tool for a Narrow Therapeutic Index Drug: Toward a Platform Approach Across Lab and Pilot Scales for Development of a Powder Blending Monitoring Method and Endpoint Determination. AAPS J, 2022. 24(6): p. 103.
79. Wang, J. and N. Takiar, Scientific Considerations for Stability Studies of Drug Substances Supporting Abbreviated New Drug Applications (ANDAs). AAPS J, 2022. 24(5): p. 94.
80. Bano, N., et al., Considerations in the Immunogenicity Assessment Strategy for Oligonucleotide Therapeutics (ONTs). AAPS J, 2022. 24(5): p. 93.
81. Meena Harish Jain, K., H.H. Hou, and R.A. Siegel, An Artificial Gut/Absorption Simulator: Description, Modeling, and Validation Using Caffeine. AAPS J, 2022. 24(5): p. 87.
82. Fernandez-Metzler, C., et al., Biomarker Assay Validation by Mass Spectrometry. AAPS J, 2022. 24(3): p. 66.
83. Hays, A., et al., Is Incurred Sample Reanalysis (ISR) Applicable in Biomarker Assays? AAPS J, 2022. 24(3): p. 65.
84. Wu, Y., et al., Prediction of glomerular filtration rate maturation across preterm and term neonates and young infants using inulin as marker. AAPS J, 2022. 24(2): p. 38.
85. Hays, A., et al., Best Practices in qPCR and dPCR Validation in Regulated Bioanalytical Laboratories. AAPS J, 2022. 24(2): p. 36.
86. Verch, T., et al., Analytical Quality by Design, Life Cycle Management, and Method Control. AAPS J, 2022. 24(1): p. 34.
87. Keire, D.A., et al., International Regulatory Collaboration on the Analysis of Nitrosamines in Metformin-Containing Medicines. AAPS J, 2022. 24(3): p. 56.
88. Zheng, J., et al., A Full Evaporation Static Headspace Gas Chromatography Method with Nitrogen Phosphorous Detection for Ultrasensitive Analysis of Semi-volatile Nitrosamines in Pharmaceutical Products. AAPS J, 2022. 24(1): p. 23.
89. Kolluri, S., et al., Machine Learning and Artificial Intelligence in Pharmaceutical Research and Development: a Review. AAPS J, 2022. 24(1): p. 19.
90. Nagy, B., et al., Application of Artificial Neural Networks in the Process Analytical Technology of Pharmaceutical Manufacturing-a Review. AAPS J, 2022. 24(4): p. 74.
91. Wu, K., et al., Machine Learning Prediction of Clinical Trial Operational Efficiency. AAPS J, 2022. 24(3): p. 57.
92. Yeoh, T., et al., Semisolid Pharmaceutical Product Characterization Using Non-invasive X-ray Microscopy and AI-Based Image Analytics. AAPS J, 2022. 24(3): p. 46.
93. Mrsny, R.J., Does an Intradermal Vaccination for Monkeypox Make Sense? AAPS J, 2022. 24(6): p. 104.
94. Popkin, M.E., et al., Chemistry Manufacturing and Controls Development, Industry Reflections on Manufacture, and Supply of Pandemic Therapies and Vaccines. AAPS J, 2022. 24(6): p. 101.
95. Zhang, P., et al., Usage of Compartmental Models in Predicting COVID-19 Outbreaks. AAPS J, 2022. 24(5): p. 98.
96. Kolli, A.R., et al., Pulmonary Delivery of Aerosolized Chloroquine and Hydroxychloroquine to Treat COVID-19: In Vitro Experimentation to Human Dosing Predictions. AAPS J, 2022. 24(1): p. 33.
97. Salimi-Moosavi, H. and M. Soto, A Non-radiometric Approach to Determine Tissue Vascular Blood Volume in Biodistribution Studies. AAPS J, 2022. 24(6): p. 116.
98. Kuo, H.D., et al., DNA Methylome and Transcriptome Study of Triterpenoid CDDO in TPA-Mediated Skin Carcinogenesis Model. AAPS J, 2022. 24(6): p. 115.
99. Printz, M.A., et al., Risk Factors, Hyaluronidase Expression, and Clinical Immunogenicity of Recombinant Human Hyaluronidase PH20, an Enzyme Enabling Subcutaneous Drug Administration. AAPS J, 2022. 24(6): p. 110.
100. Allen-Coyle, T.J., et al., FOLFIRINOX Pharmacodynamic Interactions in 2D and 3D Pancreatic Cancer Cell Cultures. AAPS J, 2022. 24(6): p. 108.
101. Sandoval, P., et al., Sinusoidal Organic Anion-Transporting Polypeptide 1B1/1B3 and Bile Canalicular Multidrug Resistance-Associated Protein 2 Play an Essential Role in the Hepatobiliary Disposition of a Synthetic Cyclic Dinucleotide (STING Agonist). AAPS J, 2022. 24(6): p. 99.
102. Kamble, S.H., et al., Metabolism of Speciociliatine, an Overlooked Kratom Alkaloid for its Potential Pharmacological Effects. AAPS J, 2022. 24(5): p. 86.
103. Noh, K., et al., Significance of the Vitamin D Receptor on Crosstalk with Nuclear Receptors and Regulation of Enzymes and Transporters. AAPS J, 2022. 24(4): p. 71.
104. Preiss, L.C., et al., Multi-Well Array Culture of Primary Human Hepatocyte Spheroids for Clearance Extrapolation of Slowly Metabolized Compounds. AAPS J, 2022. 24(2): p. 41.
105. Wang, L., et al., Nfe2l2 Regulates Metabolic Rewiring and Epigenetic Reprogramming in Mediating Cancer Protective Effect by Fucoxanthin. AAPS J, 2022. 24(1): p. 30.