Encapsulation of Risperidone by Methylated β-Cyclodextrins: Physicochemical and Molecular Modeling Studies

Risperidone (RSP) is an atypical antipsychotic drug which acts as a potent antagonist of serotonin-2 (5TH2) and dopamine-2 (D2) receptors in the brain; it is used to treat schizophrenia, behavioral and psychological symptoms of dementia and irritability associated with autism. It is a poorly water soluble benzoxazole derivative with high lipophilicity. Supramolecular adducts between drug substance and two methylated β-cyclodextrins, namely heptakis(2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD) and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TM-β-CD) were obtained in order to enhance RSP solubility and improve its biopharmaceutical profile. The inclusion complexes were evaluated by means of thermoanalytical methods (TG—thermogravimetry/DTG—derivative thermogravimetry/HF—heat flow), powder X-ray diffractometry (PXRD), universal-attenuated total reflectance Fourier transform infrared (UATR-FTIR), UV spectroscopy and saturation solubility studies. Job’s method was employed for the determination of the stoichiometry of the inclusion complexes, which was found to be 2:1 for both guest–host systems. Molecular modeling studies were carried out for an in-depth characterization of the interaction between drug substance and cyclodextrins (CDs). The physicochemical properties of the supramolecular systems differ from those of RSP, demonstrating the inclusion complex formation between drug and CDs. The RSP solubility was enhanced as a result of drug encapsulation in the CDs cavity, the higher increase being obtained with DM-β-CD as host; the guest–host system RSP/DM-β-CD can thus be a starting point for further research in developing new formulations containing RSP, with enhanced bioavailability.     

Betulonic acid—cyclodextrins inclusion complexes

Journal of Thermal Analysis and Calorimetry - Betulonic acid (BA) is a pentacyclic lupane-type triterpenoid possessing valuable pharmacological activities, exhibiting very low water solubility....     

Compatibility studies with pharmaceutical excipients for aripiprazole–heptakis (2,6-di-O-methyl)-β-cyclodextrin supramolecular adduct

Journal of Thermal Analysis and Calorimetry - Aripiprazole (ARP) is one of the newest antipsychotic drugs, exhibiting very low aqueous solubility and high lipophilicity. Considering the necessity...     

Risperidone/Randomly Methylated β-Cyclodextrin Inclusion Complex—Compatibility Study with Pharmaceutical Excipients

Risperidone (RSP) is an atypical antipsychotic drug used in treating schizophrenia, behavioral, and psychological symptoms of dementia and irritability associated with autism. The drug substance is practically insoluble in water and exhibits high lipophilicity. It also presents incompatibilities with pharmaceutical excipients such as magnesium stearate, lactose, and cellulose microcrystalline. RSP encapsulation by randomly methylated β-cyclodextrin (RM-β-CD) was performed in order to enhance drug solubility and stability and improve its biopharmaceutical profile. The inclusion complex formation was evaluated using thermal methods, powder X-ray diffractometry (PXRD), universal-attenuated total reflectance Fourier transform infrared (UATR-FTIR), UV spectroscopy, and saturation solubility studies. The 1:1 stoichiometry ratio and the apparent stability constant of the inclusion complex were determined by means of the phase solubility method. The compatibility between the supramolecular adduct and pharmaceutical excipients starch, anhydrous lactose, magnesium stearate, and cellulose microcrystalline was studied employing thermoanalytical tools (TG-thermogravimetry/DTG-derivative thermogravimetry/HF-heat flow) and spectroscopic techniques (UATR-FTIR, PXRD). The compatibility study reveals that there are no interactions between the supramolecular adduct with starch, magnesium stearate, and cellulose microcrystalline, while incompatibility with anhydrous lactose is observed even under ambient conditions. The supramolecular adduct of RSP with RM-β-CD represents a valuable candidate for further research in developing new formulations with enhanced bioavailability and stability, and the results of this study allow a pertinent selection of three excipients that can be incorporated in solid dosage forms.     

Physicochemical characterization and molecular modeling study of host–guest systems of aripiprazole and functionalized cyclodextrins

Journal of Thermal Analysis and Calorimetry - Aripiprazole (ARP), an innovative atypical antipsychotic drug, exhibits very low aqueous solubility, affecting its dissolution and absorption and high...