Cyclodextrins: Enhancing Drug Delivery, Solubility and Bioavailability for Modern Therapeutics
Abstract
:1. Introduction
2. The Effect of Cyclodextrins over the Encapsulated Active Substance
2.1. Changes in Physical-Chemical Properties
2.2. Change in Solubility
2.2.1. Mechanism of Action of Cyclodextrins in Improving Solubility
2.2.2. Impact on Bioavailability
- Oral formulations
- Ophthalmic formulations
- Parenteral formulations
- Solutions for chronic diseases
2.3. A Reduction in Side Effects
2.3.1. Stabilizing and Protecting the Drug
2.3.2. Controlled Release of the Drug
2.4. Reducing Local Toxicity
2.5. Detoxifying Active Compounds
3. Pharmaceutical Forms with Cyclodextrins
3.1. Tablets
3.2. Capsules
Active Substance | Trade Name | Cyclodextrin | Effect of Cyclodextrin | Indication | Reference |
---|---|---|---|---|---|
4-Androstenediol | Androtest | HP-β-CD | Better water solubility of inclusion complex, increased bioavailability | Supplement | [88] |
Benexate HCl | Ulgut, Lonmiel | β-CD | Increase in solubility and strong antiulcer activity | Gastritis | [89] |
Curcumin extract | Curcumin Extract 45 | γ-CD | Improved absorption of curcuminoids and bioavailability | Supplement | [90] |
Fingolimod | Fingolimod beta | β-CD | Up to 20x increase in solubility | Multiple sclerosis | [66,91] |
Omeprazole | Omebeta, Losamel, enteric capsule | β-CD | Improved bioavailability | Ulcers | [87] |
3.3. Powders and Granules
3.4. Oral Solutions and Suspensions
Active Substance | Trade Name | Cyclodextrin | Effect of Cyclodextrin | Indication | Reference |
---|---|---|---|---|---|
Itraconazole | Sporanox | HP-β-CD | Increase water solubility and bioavailability | Fungal infections | [103,104] |
Larotrectinib sulfate | Vitrakvi | HP-β-CD | Solubilizing agent | Pediatric cancer | [106] |
Midazolam | Ozalin | γ-CD | Increase midazolam solubility, mask bitter taste of solution | Premedication before anesthesia, in pediatric population | [107,108] |
Piroxicam | Flogene | β-CD | Increased solubility, fast absorption and improved gastric tolerability | Analgesic for pediatric use | [86,109] |
3.5. Parenteral Formulations
Active Substance | Trade Name and Formulation | Cyclodextrin | Effect of Cyclodextrin | Indication | Reference |
---|---|---|---|---|---|
Amiodarone | Nexterone intravenous solution | SBE-β-CD | Solubilizing agent. The inclusion complex solution is chemically stable upon storage time | Treatment and prophylaxis of frequently recurring ventricular fibrillation | [116] |
Aripiprazole | Abilify, solution for injection (intramuscular) | SBE-β-CD | Increased water solubility | Schizophrenia | [69,113] |
Diclofenac | Dyloject® (intramuscular and intravenous use) | HP-β-CD | Increase the solubility of the drug, resulting in less clinical thrombophlebitis | Rheumatic and non-rheumatic pain | [117,118] |
Diclofenac | Akis subcutaneous and intramuscular use) | HP-β-CD | Good stability, solubility, and bioavailability of the preparations | Rheumatic and non-rheumatic pain | [117,118] |
Fosphenytoin | Sesquient, Cerebyx | SBE-β-CD | Improved stability and solubility | Epilepsy | [114,115] |
PGE1 (Alprostadil) | Alprostadil Alphadex, Caverject intracavernous injection | α-CD | Increased stability | Buerger disease, male erectile dysfunction | [66,81,119] |
Posaconazole | Noxafil | SBE-β-CD | Improved solubility and stability | Anti-infective applications | [120] |
Progesterone | Lubion® solution for intramuscular and subcutaneous injection | HP-β-CD | Increase in the solubility of progesterone, resulting in improved bioavailability | Luteal phase support during assisted reproductive technology | [118] |
Remdesivir | Veklury, powder for solution for infusion | SBE-β-CD | Increased solubility, stability, bioavailability | COVID-19 | [81,121,122] |
Voriconazole | Vfend, powder for solution for infusion | SBE-β-CD | Increased solubility, better safety profile (no deterioration of renal function) in patients with renal failure | Fungal infections | [123,124] |
Ziprasidone mesylate | Geodon, powder for solution for injection | SBE-β-CD | Solubilizing agent | Schizophrenia | [125] |
3.6. Topical Formulations
Active Substance | Trade Name | Cyclodextrin | Effect of Cyclodextrin | Indication | Reference |
---|---|---|---|---|---|
Benzoyl peroxide | Nujevi Acne | γ-CD | Decrease drug degradation | Acne | [132] |
Dexamethasone | Glymesason, ointment | β-CD | Increased solubility up to 33 fold in a 1:1 complex | Dermatitis | [66,81] |
Metronidazole | Metrogel, gel | β-CD | Solubility enhancer | Rosacea | [135] |
Salicylic acid | Age Defying Blemish Treatment, Lipo™ CD-SA | HP-β-CD | Reduces skin irritation and stinging | Skin care | [136] |
Active Substance | Trade Name | Cyclodextrin | Effect of Cyclodextrin over the Active Substance | Indication | Reference |
---|---|---|---|---|---|
Chloramphenicol | Clorocil | Methyl-β-cyclodextrin | Increased stability | Eye infections | [137,138] |
Diclofenac | Voltaren Ophtha Eye Drops | HP-γ-CD | Drug solubility enhancer and penetration promoter, reduction in ocular toxicity | Pain and inflammation after ocular surgery and seasonal allergic conjunctivitis | [69,139] |
Lanosterol | Lanomax | HP-β-CD | Increased water solubility, improved bioavailability | Cataract therapy for dogs | [140] |
Levocabastine | Allergiflash | HP-β-CD | Solubilizing agent, increases bioavailability | Allergic conjunctivitis | [141] |
Olopatadine | Opatanol | HP-β-CD | Increases stability by preventing precipitation or crystallization | Allergic conjunctivitis | [142] |
3.7. Suppositories
3.8. Aerosols
3.9. Transdermal Patches
3.10. Nanotechnology-Based Drug Delivery Systems
4. The Use of Cyclodextrins in Various Diseases
4.1. Neurodegenerative Disorders
4.1.1. Improved Drug Delivery to the Brain
4.1.2. Niemann–Pick Disease Type C (NPC)
4.1.3. Alzheimer’s Disease
4.1.4. Parkinson’s Disease
4.1.5. A Reduction in Oxidative Stress and Neuroinflammation
4.2. Respiratory Diseases
4.2.1. Improving the Delivery of Inhalation Drugs
4.2.2. Reducing Corticosteroid Toxicity
4.2.3. Cystic Fibrosis
4.2.4. Chronic Obstructive Pulmonary Disease (COPD)
4.2.5. Reducing the Irritating Effects of Inhaled Drugs
4.3. Cancer Therapy
4.3.1. Improving Drug Solubility and Bioavailability
4.3.2. A Reduction in Toxicity Associated with Chemotherapy
4.3.3. Targeted Therapy
4.3.4. Bioactive Molecules Transport (Genes or RNA)
4.3.5. Reducing Drug Resistance
4.4. Cardiovascular Diseases
4.4.1. Reducing Cardiac Toxicity
4.4.2. Regulating Lipid Metabolism
4.4.3. Formulation of Antihypertensive Medication
4.4.4. Therapy of Heart Failure
4.4.5. Prevention of Cardiovascular Inflammation
4.5. Infectious Diseases
4.5.1. Improving the Solubility of Antibiotics
4.5.2. Side Effects Reduction
4.5.3. Targeted Drug Delivery
4.5.4. Treatment of Fungal Infections
4.5.5. Combating Drug Resistance
5. Future Perspectives
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Active Substance | Water Solubility (mg/mL) | Solubility When Associated with β-Cyclodextrin (mg/mL) | Cyclodextrin Used | Reference |
---|---|---|---|---|
Amphotericin B | 0.001 | 0.15 | β-cyclodextrin sulfobutyl ether (SBE-β-CD) | [14] |
Cefixime | 0.76 | 17.5 | SBE-β-CD | [15] |
Cefpodoxime Proxetil | 0.241 | 0.637 | β-CD | [16] |
Ceftiofur | 0.03 | 2.18 | HP-β-CD | [17] |
Dexamethasone | 0.1 | 2.5 | β-CD | [18] |
Diclofenac | 4.0 | 20.0 | HP-β-CD | [19] |
Ibuprofen | 0.1 | 10.0 | Methyl-β-cyclodextrin (M-β-CD) | [20] |
ITH12674 | 0.31 | 10.7 | HP-β-CD | [7] |
Itraconazole | 0.001 | 4–5 | HP-β-CD | [21] |
Metronidazole benzoate | 0.14 | 1.39 | β-CD | [22] |
Nifedipine | 0.02 | 1.5 | β-CD | [23] |
Paclitaxel | 0.003 | 2.0 | HP-β-CD | [24] |
Tinidazole | 3.76 | 36.89 | β-CD | [25] |
Active Substance | Trade Name and Formulation | Cyclodextrin | Effect of Cyclodextrin over the Active Substance | Indication | Reference |
---|---|---|---|---|---|
Brivaracetam | Brivlera | β-CD | Improved drug dissolution | Epilepsy | [71,72] |
Cetirizine | Zyrtec, WalZyr, Revicet One-day tablets, chewing tablets | β-CD | Higher stability against oxidative degradation of the drug, increased solubility, masking of the unpleasant bitter taste of the drug | Allergy | [66,67,73,74] |
Desloratadine | Desloratadine | β-CD | Increased stability (no coloration), minimum N-, formyl desloratadine formation | Allergy | [75] |
Ethinylestradiol/ Drospirenone | Yaz® | β-CD | Enhance water solubility | Contraception | [64,76] |
Famotidine | Famotidine OD Tablets | β-CD | Increased water solubility, mask bitter taste | Ulcer | [77] |
Nimesulide | Nimedex | β-CD | Increased water solubility and dissolution rate, leading to rapid absorption of the drug, more rapid onset of action compared to nimesulide | Pain after arthroscopic surgery | [78,79] |
Nitroglycerin | Nitropen, sublingual tablet | β-CD | Low volatility of nitroglycerine | Angina pectoris | [68,80] |
Limaprost alfadex (Prostaglandin E1 analogue) | Opalmon tablets | β-CD | Increased stability against humidity | Pain, ulcer | [66,81,82] |
Dinoprostone (Prostaglandin E2 derivative) | Prostarmon E (sublingual tablets), Dinoproston- betadex | β-CD | Increased stability, improved drug dissolution in saliva and organoleptic properties | Induction of labor | [66,81] |
Rofecoxib | Rofizgel | β-CD | Improved solubility and dissolution rate | Arthritis | [66,83,84] |
Tiaprofenic acid | Surgamyl | β-CD | Increase in solubility, absorption and bioavailability, masking bitter taste | Pain management | [85] |
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Nicolaescu, O.E.; Belu, I.; Mocanu, A.G.; Manda, V.C.; Rău, G.; Pîrvu, A.S.; Ionescu, C.; Ciulu-Costinescu, F.; Popescu, M.; Ciocîlteu, M.V. Cyclodextrins: Enhancing Drug Delivery, Solubility and Bioavailability for Modern Therapeutics. Pharmaceutics 2025, 17, 288. https://doi.org/10.3390/pharmaceutics17030288
Nicolaescu OE, Belu I, Mocanu AG, Manda VC, Rău G, Pîrvu AS, Ionescu C, Ciulu-Costinescu F, Popescu M, Ciocîlteu MV. Cyclodextrins: Enhancing Drug Delivery, Solubility and Bioavailability for Modern Therapeutics. Pharmaceutics. 2025; 17(3):288. https://doi.org/10.3390/pharmaceutics17030288
Chicago/Turabian StyleNicolaescu, Oana Elena, Ionela Belu, Andreea Gabriela Mocanu, Valentin Costel Manda, Gabriela Rău, Andreea Silvia Pîrvu, Cătălina Ionescu, Felicia Ciulu-Costinescu, Mariana Popescu, and Maria Viorica Ciocîlteu. 2025. "Cyclodextrins: Enhancing Drug Delivery, Solubility and Bioavailability for Modern Therapeutics" Pharmaceutics 17, no. 3: 288. https://doi.org/10.3390/pharmaceutics17030288
APA StyleNicolaescu, O. E., Belu, I., Mocanu, A. G., Manda, V. C., Rău, G., Pîrvu, A. S., Ionescu, C., Ciulu-Costinescu, F., Popescu, M., & Ciocîlteu, M. V. (2025). Cyclodextrins: Enhancing Drug Delivery, Solubility and Bioavailability for Modern Therapeutics. Pharmaceutics, 17(3), 288. https://doi.org/10.3390/pharmaceutics17030288