{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:29:13Z","timestamp":1790710153455,"version":"4.1.0"},"reference-count":76,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T00:00:00Z","timestamp":1741910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of South Australia, MedTEC Pharma","award":["PG110896"],"award-info":[{"award-number":["PG110896"]}]},{"name":"University of South Australia, MedTEC Pharma","award":["PG110902"],"award-info":[{"award-number":["PG110902"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cannabidiol (CBD) has demonstrated therapeutic potential in treating epilepsy, multiple sclerosis, Alzheimer\u2019s, Parkinson\u2019s, and Crohn\u2019s diseases. Despite its promising effects and analgesic, anti-inflammatory, and anxiolytic properties, oral CBD\u2019s full potential is hindered by poor water solubility (0.7\u201310 \u03bcg\/mL), low permeability, and chemical instability. This study aimed to enhance CBD\u2019s dissolution, stability, and gastrointestinal (GI) permeability by forming a CBD\u2013phospholipid complex (CBD-PLC). We hypothesised that CBD-PLC would enhance CBD\u2019s hydrophilicity, thus improving GI barrier permeability. This study involved screening an optimal phospholipid (PL) using a Design of Experiments (DoE) approach to prepare CBD-PLC with nanosized droplets (194.3 nm). Dissolution studies revealed significantly enhanced release rates for CBD-PLC\u201444.7% at 2 h and 67.1% at 3 h\u2014compared to 0% for pure CBD and 7.2% for a physical mixture (PM). Cellular uptake studies showed that at 30 \u00b5M, CBD-PLC exhibited 32.7% higher apparent permeability coefficients (Papp), nearly doubling at 40 \u00b5M compared to pure CBD. Cytotoxicity tests confirmed safety over 24 h, while 12-month stability tests demonstrated consistent performance under varied conditions. The results indicate that CBD-PLC improves CBD\u2019s solubility, permeability, and stability, offering a promising strategy to address the limitations of oral CBD delivery systems.<\/jats:p>","DOI":"10.3390\/ijms26062647","type":"journal-article","created":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T13:07:51Z","timestamp":1741957671000},"page":"2647","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Optimising Cannabidiol Delivery: Improving Water Solubility and Permeability Through Phospholipid Complexation"],"prefix":"10.3390","volume":"26","author":[{"given":"Thabata","family":"Muta","sequence":"first","affiliation":[{"name":"Centre for Pharmaceutical Innovation (CPI), Clinical & Health Science, University of South Australia, Adelaide, SA 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riya","family":"Khetan","sequence":"additional","affiliation":[{"name":"Centre for Pharmaceutical Innovation (CPI), Clinical & Health Science, University of South Australia, Adelaide, SA 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0008-5895","authenticated-orcid":false,"given":"Yunmei","family":"Song","sequence":"additional","affiliation":[{"name":"Centre for Pharmaceutical Innovation (CPI), Clinical & Health Science, University of South Australia, Adelaide, SA 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7253-2629","authenticated-orcid":false,"given":"Sanjay","family":"Garg","sequence":"additional","affiliation":[{"name":"Centre for Pharmaceutical Innovation (CPI), Clinical & Health Science, University of South Australia, Adelaide, SA 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1007\/s40429-020-00326-8","article-title":"Therapeutic Efficacy of Cannabidiol (CBD): A Review of the Evidence from Clinical Trials and Human Laboratory Studies","volume":"7","author":"Sholler","year":"2020","journal-title":"Curr. Addict. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Knaub, K., Sartorius, T., Dharsono, T., Wacker, R., Wilhelm, M., and Schon, C. (2019). A Novel Self-Emulsifying Drug Delivery System (SEDDS) Based on VESIsorb((R)) Formulation Technology Improving the Oral Bioavailability of Cannabidiol in Healthy Subjects. Molecules, 24.","DOI":"10.3390\/molecules24162967"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.1056\/NEJMoa1611618","article-title":"Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome","volume":"376","author":"Devinsky","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1016\/S0140-6736(18)30136-3","article-title":"Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): A randomised, double-blind, placebo-controlled phase 3 trial","volume":"391","author":"Thiele","year":"2018","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1001\/jamaneurol.2020.4607","article-title":"Add-on Cannabidiol Treatment for Drug-Resistant Seizures in Tuberous Sclerosis Complex: A Placebo-Controlled Randomized Clinical Trial","volume":"78","author":"Thiele","year":"2021","journal-title":"JAMA Neurol."},{"key":"ref_6","unstructured":"(2024, May 27). Cannabidiol (CBD) Market Size, Share & Industry Analysis, By Source (Marijuana and Hemp), Application (Food & Beverages, Pharmaceuticals, Pet Care, Cosmetics and Others), and Regional Forecast, 2024\u20132032. Available online: https:\/\/www.fortunebusinessinsights.com\/segmentation\/cannabidiol-cbd-market-103215."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1016\/S0090-9556(25)07058-8","article-title":"Pharmacokinetics of the dimethylheptyl homolog of cannabidiol in dogs","volume":"16","author":"Samara","year":"1988","journal-title":"Drug Metab. Dispos."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.brainres.2007.09.090","article-title":"Cannabidiol potentiates pharmacological effects of Delta(9)-tetrahydrocannabinol via CB(1) receptor-dependent mechanism","volume":"1188","author":"Hayakawa","year":"2008","journal-title":"Brain Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.ejpb.2020.06.021","article-title":"Pharmacokinetic investigation of synthetic cannabidiol oral formulations in healthy volunteers","volume":"154","author":"Izgelov","year":"2020","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Millar, S.A., Stone, N.L., Yates, A.S., and O\u2019Sullivan, S.E. (2018). A Systematic Review on the Pharmacokinetics of Cannabidiol in Humans. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.01365"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1002\/cpdd.408","article-title":"Single-Dose Pharmacokinetics of Oral Cannabidiol Following Administration of PTL101: A New Formulation Based on Gelatin Matrix Pellets Technology","volume":"7","author":"Atsmon","year":"2018","journal-title":"Clin. Pharmacol. Drug Dev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1002\/ptr.6651","article-title":"Evaluation of pharmacokinetics and acute anti-inflammatory potential of two oral cannabidiol preparations in healthy adults","volume":"34","author":"Hobbs","year":"2020","journal-title":"Phytother. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1097\/j.pain.0000000000001896","article-title":"A randomized, double-blind, placebo-controlled study of daily cannabidiol for the treatment of canine osteoarthritis pain","volume":"161","author":"Verrico","year":"2020","journal-title":"Pain."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"O\u2019Sullivan, S.E., Jensen, S.S., Kolli, A.R., Nikolajsen, G.N., Bruun, H.Z., and Hoeng, J. (2024). Strategies to Improve Cannabidiol Bioavailability and Drug Delivery. Pharmaceuticals, 17.","DOI":"10.3390\/ph17020244"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Hossain, K.R., Alghalayini, A., and Valenzuela, S.M. (2023). Current Challenges and Opportunities for Improved Cannabidiol Solubility. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241914514"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"S\u00f6pper, U., Hoffmann, A., and Daniels, R. (2021). Mucoadhesion and Mucopenetration of Cannabidiol (CBD)-Loaded Mesoporous Carrier Systems for Buccal Drug Delivery. Sci. Pharm., 89.","DOI":"10.3390\/scipharm89030035"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.jddst.2017.03.027","article-title":"Phospholipids: Unique carriers for drug delivery systems","volume":"39","author":"Singh","year":"2017","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1007\/s13346-020-00822-4","article-title":"Phospholipid complex-loaded self-assembled phytosomal soft nanoparticles: Evidence of enhanced solubility, dissolution rate, ex vivo permeability, oral bioavailability, and antioxidant potential of mangiferin","volume":"11","author":"Telange","year":"2021","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_19","first-page":"17","article-title":"Phytosome and liposome: The beneficial encapsulation systems in drug delivery and food application","volume":"2","author":"Karimi","year":"2015","journal-title":"Appl. Food Biotechnol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/s40199-021-00403-x","article-title":"Colloidal and vesicular delivery system for herbal bioactive constituents","volume":"29","author":"Pandey","year":"2021","journal-title":"Daru"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"17","DOI":"10.2174\/157016312799304507","article-title":"Quercetin-phospholipid complex: An amorphous pharmaceutical system in herbal drug delivery","volume":"9","author":"Singh","year":"2012","journal-title":"Curr. Drug Discov. Technol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1007\/s40265-021-01579-x","article-title":"Cannabinoid Formulations and Delivery Systems: Current and Future Options to Treat Pain","volume":"81","author":"Stella","year":"2021","journal-title":"Drugs"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1080\/10717544.2019.1686086","article-title":"Mechanisms of oral absorption improvement for insoluble drugs by the combination of phospholipid complex and SNEDDS","volume":"26","author":"Tong","year":"2019","journal-title":"Drug Deliv."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"14884","DOI":"10.1021\/acs.jafc.0c06383","article-title":"Phosphatidylcholine Ameliorates LPS-Induced Systemic Inflammation and Cognitive Impairments via Mediating the Gut-Brain Axis Balance","volume":"68","author":"Tan","year":"2020","journal-title":"J. Agric. Food Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1615\/CritRevTherDrugCarrierSyst.2013005964","article-title":"Drug carrier systems for solubility enhancement of BCS class II drugs: A critical review","volume":"30","author":"Kumar","year":"2013","journal-title":"Crit. Rev. Ther. Drug Carr. Syst."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.jconrel.2016.07.051","article-title":"Role of nanoparticle size, shape and surface chemistry in oral drug delivery","volume":"238","author":"Banerjee","year":"2016","journal-title":"J. Control Release"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"102254","DOI":"10.1016\/j.jddst.2020.102254","article-title":"A novel nanosized phospholipid complex of Biochanin A for improving oral bioavailability: Preparation and in-vitro\/in-vivo characterizations","volume":"61","author":"Singh","year":"2021","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.ejps.2019.02.006","article-title":"Enhanced transdermal permeation and anti-inflammatory potential of phospholipids complex-loaded matrix film of umbelliferone: Formulation development, physico-chemical and functional characterization","volume":"131","author":"Telange","year":"2019","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/S0378-5173(98)00092-1","article-title":"Effect of light and temperature on zeta potential and physical stability in solid lipid nanoparticle (SLN\u2122) dispersions","volume":"168","author":"Freitas","year":"1998","journal-title":"Int. J. Pharm."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"35","DOI":"10.15171\/apb.2017.005","article-title":"Phospholipid Complex Technique for Superior Bioavailability of Phytoconstituents","volume":"7","author":"Gnananath","year":"2017","journal-title":"Adv. Pharm. Bull."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"839","DOI":"10.31557\/APJCP.2024.25.3.839","article-title":"A Comparative Analysis on the Potential Anticancer Properties of Tetrahydrocannabinol, Cannabidiol, and Tetrahydrocannabivarin Compounds Through In Silico Approach","volume":"25","author":"Gallardo","year":"2024","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Daina, A., Michielin, O., and Zoete, V. (2017). SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep., 7.","DOI":"10.1038\/srep42717"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/s10847-009-9705-8","article-title":"Preparation and characterization of phospholipid complexes of naringenin for effective drug delivery","volume":"67","author":"Semalty","year":"2010","journal-title":"J. Incl. Phenom. Macrocycl. Chem."},{"key":"ref_34","first-page":"4169","article-title":"Preparation and characterization of tetrandrine-phospholipid complex loaded lipid nanocapsules as potential oral carriers","volume":"8","author":"Zhao","year":"2013","journal-title":"Int. J. Nanomed."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"118567","DOI":"10.1016\/j.ijpharm.2019.118567","article-title":"The effect of the saturation degree of phospholipid on the formation of a novel self-assembled nano-micellar complex carrier with enhanced intestinal permeability","volume":"569","author":"Ahmed","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"210","DOI":"10.3390\/nutraceuticals3020016","article-title":"Nanostructured Lipid Carriers Loaded with Cannabidiol Enhance Its Bioaccessibility to the Small Intestine","volume":"3","author":"Grifoni","year":"2023","journal-title":"Nutraceuticals"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"118698","DOI":"10.1016\/j.ijpharm.2019.118698","article-title":"Phospholipid-based complex of raloxifene with enhanced biopharmaceutical potential: Synthesis, characterization and preclinical assessment","volume":"571","author":"Jain","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Singh, M., Singh, C., Sarasija, S., Roy, S., and Banerjee, U. (2022). Exploring the Effects of Processing Methods on Telmisartan-Phospholipid Complex: A Comparative Study. ChemRxiv.","DOI":"10.26434\/chemrxiv-2022-4w95p"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Millar, S.A., Maguire, R.F., Yates, A.S., and O\u2019Sullivan, S.E. (2020). Towards Better Delivery of Cannabidiol (CBD). Pharmaceuticals, 13.","DOI":"10.3390\/ph13090219"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Tong, Y., Shi, W., Zhang, Q., and Wang, J. (2023). Preparation, Characterization, and In Vivo Evaluation of Gentiopicroside-Phospholipid Complex (GTP-PC) and Its Self-Nanoemulsion Drug Delivery System (GTP-PC-SNEDDS). Pharmaceuticals, 16.","DOI":"10.3390\/ph16010099"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Shilo-Benjamini, Y., Cern, A., Zilbersheid, D., Hod, A., Lavy, E., Barasch, D., and Barenholz, Y. (2022). A Case Report of Subcutaneously Injected Liposomal Cannabidiol Formulation Used as a Compassion Therapy for Pain Management in a Dog. Front. Vet. Sci., 9.","DOI":"10.3389\/fvets.2022.892306"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Moqejwa, T., Marimuthu, T., Kondiah, P.P.D., and Choonara, Y.E. (2022). Development of Stable Nano-Sized Transfersomes as a Rectal Colloid for Enhanced Delivery of Cannabidiol. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14040703"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1111\/1750-3841.15677","article-title":"Nanoliposomes for encapsulation and calcium delivery of egg white peptide-calcium complex","volume":"86","author":"Zhang","year":"2021","journal-title":"J. Food Sci."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Stefkov, G., Cvetkovikj Karanfilova, I., Stoilkovska Gjorgievska, V., Trajkovska, A., Geskovski, N., Karapandzova, M., and Kulevanova, S. (2022). Analytical Techniques for Phytocannabinoid Profiling of Cannabis and Cannabis-Based Products-A Comprehensive Review. Molecules, 27.","DOI":"10.3390\/molecules27030975"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s12247-024-09884-0","article-title":"An Investigation into the Preparation, Characterization, and Therapeutic Applications of Novel Gefitinib\/Capric Acid Deep Eutectic Systems","volume":"19","author":"Alkhawaja","year":"2024","journal-title":"J. Pharm. Innov."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Citti, C., Linciano, P., Panseri, S., Vezzalini, F., Forni, F., Vandelli, M.A., and Cannazza, G. (2019). Cannabinoid Profiling of Hemp Seed Oil by Liquid Chromatography Coupled to High-Resolution Mass Spectrometry. Front. Plant Sci., 10.","DOI":"10.3389\/fpls.2019.00120"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4700","DOI":"10.1039\/D1NJ05998J","article-title":"Cannabidiol\/hydroxypropyl-\u03b2-cyclodextrin inclusion complex: Structure analysis, release behavior, permeability, and bioactivity under in vitro digestion","volume":"46","author":"Li","year":"2022","journal-title":"New J. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"116070","DOI":"10.1016\/j.molliq.2021.116070","article-title":"Inclusion complexes of cannabidiol with \u03b2-cyclodextrin and its derivative: Physicochemical properties, water solubility, and antioxidant activity","volume":"334","author":"Li","year":"2021","journal-title":"J. Mol. Liq."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.talanta.2015.02.040","article-title":"1H NMR and HPLC\/DAD for Cannabis sativa L. chemotype distinction, extract profiling and specification","volume":"140","author":"Peschel","year":"2015","journal-title":"Talanta"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Barthlott, I., Scharinger, A., Golombek, P., Kuballa, T., and Lachenmeier, D.W. (2021). A Quantitative 1H NMR Method for Screening Cannabinoids in CBD Oils. Toxics, 9.","DOI":"10.20944\/preprints202105.0393.v1"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"12137","DOI":"10.1021\/acs.jmedchem.0c00724","article-title":"The Essential Medicinal Chemistry of Cannabidiol (CBD)","volume":"63","author":"Nelson","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Morales, P., Reggio, P.H., and Jagerovic, N. (2017). An Overview on Medicinal Chemistry of Synthetic and Natural Derivatives of Cannabidiol. Front. Pharmacol., 8.","DOI":"10.3389\/fphar.2017.00422"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1021\/om0611608","article-title":"Organobismuth(III) Dihalides with T-Shaped Geometry Stabilized by Intramolecular N\u2192Bi Interactions and Related Diorganobismuth(III) Halides","volume":"26","author":"Soran","year":"2007","journal-title":"Organometallics"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1111\/1541-4337.12138","article-title":"An Overview on Nondestructive Spectroscopic Techniques for Lipid and Lipid Oxidation Analysis in Fish and Fish Products","volume":"14","author":"Xu","year":"2015","journal-title":"Compr. Rev. Food Sci. Food Saf."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.ijpharm.2014.01.023","article-title":"Solid dispersion of berberine-phospholipid complex\/TPGS 1000\/SiO2: Preparation, characterization and in vivo studies","volume":"465","author":"Zhang","year":"2014","journal-title":"Int J Pharm"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.ijpharm.2014.03.023","article-title":"Solid phospholipid nano-particles: Investigations into formulation and dissolution properties of griseofulvin","volume":"467","year":"2014","journal-title":"Int. J. Pharm."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3870","DOI":"10.1021\/acs.molpharmaceut.0c00614","article-title":"Hierarchical Mass Transfer Analysis of Drug Particle Dissolution, Highlighting the Hydrodynamics, pH, Particle Size, and Buffer Effects for the Dissolution of Ionizable and Nonionizable Drugs in a Compendial Dissolution Vessel","volume":"17","author":"Salehi","year":"2020","journal-title":"Mol. Pharm."},{"key":"ref_58","unstructured":"Convention, U.S.P. (2022). Capsules\u2014Dissolution Testing and Related Quality Attributes. United States Pharmacopeia and National Formulary (USP-NF), United States Pharmacopeial Convention. [The Latest Edition or Specify as \u201cUSP 2022\u201d ed.]."},{"key":"ref_59","unstructured":"U.S. Food and Drug Administration (2006). Guidance for Industry: Investigating Out-of-Specification (OOS) Test Results for Pharmaceutical Production, U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER)."},{"key":"ref_60","unstructured":"(TGA), T.G.A. (2021). ARGOM Appendix 2: Guidelines on Quality Aspects of OTC Applications: 7, Control of Finished Product. Australian Government Department of Health."},{"key":"ref_61","unstructured":"Standard, I. (2009). Biological Evaluation of Medical Devices\u2014Part 5: Tests for In Vitro Cytotoxicity, International Organization for Standardization."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1111\/j.1365-2036.1989.tb00254.x","article-title":"pH-profile and regional transit times of the normal gut measured by a radiotelemetry device","volume":"3","author":"Fallingborg","year":"1989","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1021\/mp5005806","article-title":"Mechanism of enhanced oral absorption of morin by phospholipid complex based self-nanoemulsifying drug delivery system","volume":"12","author":"Zhang","year":"2015","journal-title":"Mol. Pharm."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/S0887-2333(97)00026-X","article-title":"Rapid decrease in transepithelial electrical resistance of human intestinal Caco-2 cell monolayers by cytotoxic membrane perturbents","volume":"11","author":"Narai","year":"1997","journal-title":"Toxicol. Vitr."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.ejps.2005.01.001","article-title":"Effect of self-microemulsifying drug delivery systems containing Labrasol on tight junctions in Caco-2 cells","volume":"24","author":"Sha","year":"2005","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Cocetta, V., Governa, P., Borgonetti, V., Tinazzi, M., Peron, G., Catanzaro, D., Berretta, M., Biagi, M., Manetti, F., and Dall\u2019Acqua, S. (2021). Cannabidiol Isolated From Cannabis sativa L. Protects Intestinal Barrier From In Vitro Inflammation and Oxidative Stress. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.641210"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Abdella, S., Kim, S., Afinjuomo, O., Song, Y., Upton, R., and Garg, S. (2023). Harnessing the Synergistic Potential of 3D Printed Buccal Films and Nanostructured Lipid Carriers (NLCs) For Personalised Cannabidiol Delivery, Research Square.","DOI":"10.21203\/rs.3.rs-2945517\/v1"},{"key":"ref_68","first-page":"916","article-title":"Development of liquiritigenin-phospholipid complex with the enhanced oral bioavailability","volume":"18","author":"Shi","year":"2020","journal-title":"Chin. J. Nat. Med."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Gosty\u0144ska, A., Czerniel, J., Ku\u017ami\u0144ska, J., Brzozowski, J., Majchrzak-Celi\u0144ska, A., Krajka-Ku\u017aniak, V., and Stawny, M. (2023). Honokiol-Loaded Nanoemulsion for Glioblastoma Treatment: Statistical Optimization, Physicochemical Characterization, and an In Vitro Toxicity Assay. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15020448"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Pu, Y., Zhang, X., Zhang, Q., Wang, B., Chen, Y., Zang, C., Wang, Y., Dong, T.T.-X., and Zhang, T. (2016). 20(S)-Protopanaxadiol Phospholipid Complex: Process Optimization, Characterization, In Vitro Dissolution and Molecular Docking Studies. Molecules, 21.","DOI":"10.3390\/molecules21101396"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"105212","DOI":"10.1016\/j.ejps.2020.105212","article-title":"Phytosome-nanosuspensions for silybin-phospholipid complex with increased bioavailability and hepatoprotection efficacy","volume":"144","author":"Chi","year":"2020","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Volmajer, J., Persin, Z., Voncina, B., Vrezner, K., Tu\u0161ek, L., and Zemlji\u010d, L. (2020). Microencapsulation of Cannabidiol in Liposomes as Coating for Cellulose for Potential Advanced Sanitary Material. Coatings, 11.","DOI":"10.3390\/coatings11010003"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.cis.2018.01.003","article-title":"Prodrugs, phospholipids and vesicular delivery\u2014An effective triumvirate of pharmacosomes","volume":"253","author":"Kapoor","year":"2018","journal-title":"Adv. Colloid. Interface Sci."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Wang, M., You, S.K., Lee, H.K., Han, M.G., Lee, H.M., Pham, T.M.A., Na, Y.G., and Cho, C.W. (2020). Development and Evaluation of Docetaxel-Phospholipid Complex Loaded Self-Microemulsifying Drug Delivery System: Optimization and In Vitro\/Ex Vivo Studies. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12060544"},{"key":"ref_75","unstructured":"(ICH) (2003). Stability Testing of New Drug Substances and Products: Q1A(R2), ICH."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1159\/000517120","article-title":"The Pharmacological Effects of Plant-Derived versus Synthetic Cannabidiol in Human Cell Lines","volume":"4","author":"Maguire","year":"2021","journal-title":"Med. 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