title: Fast dissolving drug-drug eutectics with improved compressibility and synergistic effects.
abstract: Combinational therapy has become increasingly popular in recent times due to various advantages like greater therapeutic effect, reduced number of prescriptions, lower administrative costs, and an increase in patient compliance. Drug-drug multicomponent adducts could help in combination of drugs at supramolecular level. Two drug-drug eutectics of etodolac with paracetamol (EP) and etodolac with propranolol hydrochloride (EPHC) were successfully designed and synthesized for the first time. These eutectics significantly improved dissolution and material properties. A 6 to 9 fold enhancement in % dissolution efficiency was found at 1min suggesting the fast dissolving capabilities of the eutectic mixtures when compared to plain drug. In addition, eutectic mixtures have shown improved hardness compared to plain drugs. EP and EPHC have shown around 5 fold and 3 fold improvements in hardness respectively at 10MPa when compared to plain etodolac. Cell culture studies have shown improved effects of EP. Western blotting analysis revealed that the said combination successfully reduced various inflammatory mediators like TNF-α, COX-2 and IL-6. Whereas, the eutectic combination EPHC has shown enhanced cytotoxic effects with synergistic combination index and favorable dose reduction index. The generated multi-component systems EP and EPHC with fast dissolving capabilities, improved hardness at lower pressures and synergistic effects represent prospective combinations for effective treatment of osteoarthritis and cancer chemotherapy respectively.
authors.affiliation: Solid State Pharmaceutical Research Group (SSPRG), , Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Hyderabad, India.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Thipparaboina
authors.affiliation: Department of Pharmacology, National Institute of Pharmaceutical Education and Research, Hyderabad, India.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Thumuri
authors.affiliation: Solid State Pharmaceutical Research Group (SSPRG), , Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Hyderabad, India.
authors.forename: Rahul
authors.initials: R
authors.lastname: Chavan
authors.affiliation: Department of Pharmacology, National Institute of Pharmaceutical Education and Research, Hyderabad, India.
authors.forename: V G M
authors.initials: VGM
authors.lastname: Naidu
authors.affiliation: Solid State Pharmaceutical Research Group (SSPRG), , Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Hyderabad, India. Electronic address: nalini@niperhyd.ac.in.
authors.forename: Nalini R
authors.initials: NR
authors.lastname: Shastri
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage*; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D004357:Drug Synergism; D017308:Etodolac / Q000008:administration & dosage*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D033362:Powder Diffraction; D011433:Propranolol / Q000008:administration & dosage*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D018836:Inflammation Mediators; D017308:Etodolac; D000082:Acetaminophen; D011433:Propranolol
keywords: Cocrystals; Compression; Crystal engineering; Dissolution; Etodolac; Eutectics; Paracetamol