Search

Aripiprazole (ARP) is one of the newest antipsychotic drugs, exhibiting very low aqueous solubility and high lipophilicity. Considering the necessity of improvement of ARP physicochemical properties and its biopharmaceutical profile, cyclodextrin complexation of the drug substance was performed. As selected cyclodextrin, a functionalized β-cyclodextrin was used, namely heptakis(2,6-di-O-methyl)-β-cyclodextrin (DIMEB), and the supramolecular adduct ARP/DIMEB was prepared by kneading technique and characterized using thermoanalytical tools (TG—thermogravimetry/DTG—derivative thermogravimetry/HF—heat flow), powder X-ray diffractometry patterns (PXRD), universal-attenuated total reflectance Fourier transform infrared (UATR-FTIR) and UV (ultraviolet) spectroscopy and, as well, saturation solubility studies. Job’s method was used for the stoichiometry of APR/DIMEB inclusion complex determination, which was found to be 1:2. Molecular modeling studies were complementary realized as to get a view over the way that ARP is hosted inside the cyclodextrin. The compatibility between the inclusion complex and some common pharmaceutical excipients, namely starch, magnesium stearate, lactose monohydrate, microcrystalline cellulose and methylcellulose, has been evaluated by means of thermal methods of analysis (TG/DTG/HF), UATR-FTIR spectroscopy and PXRD pattern. The preformulation data regarding the compatibility of ARP/DIMEB complex with selected excipients suggested that under ambient conditions, chemical interactions are observed solely between ARP/DIMEB inclusion complex and magnesium stearate, as indicated by the UATR-FTIR spectroscopy. The incompatibility in the system ARP/DIMEB + MgS is also confirmed by the PXRD study, this second investigational technique revealing also the advanced amorphization of components during mixing of complex with starch, microcrystalline cellulose and methylcellulose, but without indicating interactions. Later on, under thermal stress, thermally induced interactions occur between the components in the systems containing magnesium stearate and methylcellulose, while starch, microcrystalline cellulose and lactose can be safely used as excipients in developing solid formulations containing ARP/DIMEB inclusion complex as active pharmaceutical ingredient.

Aripiprazole (ARP), an innovative atypical antipsychotic drug, exhibits very low aqueous solubility, affecting its dissolution and absorption and high lipophilicity. Its complexation with cyclodextrins (CDs) was designed to improve drug solubility and consequently its bioavailability. The inclusion complexes of aripiprazole with two β-cyclodextrin derivative, namely random methyl-β-cyclodextrin (RAMEB) and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin, were obtained and investigated both in solution and in solid state. The kneading method was used to prepare the inclusion complexes, and they were characterized with different analytical techniques, including thermal analysis, powder X-ray diffractometry, universal attenuated total reflectance Fourier-transform IR spectroscopy and UV spectroscopy. The stoichiometry of both APR/CDs inclusion complexes was found as 1:2 by employing continuous variation method. Benesi–Hildebrand equation was used for the apparent constant stability determination. Structural studies of the inclusion complexes were carried out using molecular modeling techniques in order to explain the complexation mechanism. The results of the studies demonstrate that the physicochemical properties of the kneaded products are different from ARP, testifying the inclusion complexes formation between aripiprazole and CDs when the kneading method is used. The solubility of the drug substance was improved upon complexation with CDs; higher increase in ARP solubility was noticed in the presence of RAMEB.

Betulonic acid (BA) is a pentacyclic lupane-type triterpenoid possessing valuable pharmacological activities, exhibiting very low water solubility. Inclusion complexes between the substance and cyclodextrins (CDs) were obtained in order to improve its solubility and consequently its bioavailability. The aim of this study was to investigate the guest–host interaction of BA with γ-cyclodextrin (γ-CD) and its derivative, 2-hydroxypropyl-γ-cyclodextrin (HP-γ-CD), in solution and in solid state in order to prove the formation of inclusion complexes between the components. The kneading method was used for the inclusion complexes preparation, and different analytical techniques such as thermal analysis, powder X-ray diffractometry, universal attenuated total reflectance Fourier transform IR spectroscopy (UATR-FTIR) and UV spectroscopy were employed to investigate the interaction between substances. The stoichiometry of the inclusion complex BA/HP-γ-CD was found to be 1:1 by employing continuous variation method, and the apparent stability constant was calculated as 1855.55 M−1 using Benesi–Hildebrand equation. Structural studies of the inclusion complexes were carried out using molecular modeling techniques in order to explain the complexation mechanism. The results of this study confirm the formation of inclusion complexes between BA and cyclodextrins both in solution and in solid state.

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.

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 &beta, cyclodextrins, namely heptakis(2,6-di-O-methyl)-&beta, cyclodextrin (DM-&beta, CD) and heptakis(2,3,6-tri-O-methyl)-&beta, cyclodextrin (TM-&beta, 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&mdash, thermogravimetry/DTG&mdash, derivative thermogravimetry/HF&mdash, heat flow), powder X-ray diffractometry (PXRD), universal-attenuated total reflectance Fourier transform infrared (UATR-FTIR), UV spectroscopy and saturation solubility studies. Job&rsquo, s method was employed for the determination of the stoichiometry of the inclusion complexes, which was found to be 2:1 for both guest&ndash, 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-&beta, CD as host, the guest&ndash, host system RSP/DM-&beta, CD can thus be a starting point for further research in developing new formulations containing RSP, with enhanced bioavailability.

Fosinopril, the unique phosphinic acid derivative among the angiotensin-converting enzyme inhibitors, is a poorly water-soluble and highly lipophilic substance, exhibiting poor bioavailability following oral administration. The inclusion complex between the drug substance and hydroxypropyl-β-cyclodextrin (HPBCD) was obtained in order to improve its solubility and, consequently, its bioavailability. The aim of this study was to investigate the thermoanalytical behavior of fosinopril sodium (FOS), of the inclusion complex between FOS and HPBCD (FOS/HPBCD) and its physical mixture with some pharmaceutical excipients commonly used in solid dosage forms. The analytical techniques used for this purpose have been thermogravimetry/derivative thermogravimetry (TG/DTG), differential thermal analysis (DTA) and Fourier transform infrared spectroscopy (FT-IR). Non-isothermal methods have been employed to determine the kinetic parameters using DTG data. The DTA curves of inclusion complex FOS/HPBCD and its 1:1 (m/m) physical mixtures with excipients (magnesium stearate, talc and starch) indicated a possible interaction of the inclusion complex (IC) with magnesium stearate and talc. FT-IR data and the values of the activation energy (E a) for physical mixture did not evidence any incompatibility between the IC and excipients. Concerning FOS, the thermoanalytical results and the value of E a for the binary mixture of drug with magnesium stearate confirmed the incompatibility between the two substances reported in the literature. Therefore, as a result of the encapsulation of FOS in the HPBCD cavity, the stabilization of drug substance in the presence of magnesium stearate has been realized.

Zofenopril calcium (ZOF)is one of the newest angiotensin converting enzyme (ACE) inhibitor, is one of the highly lipophilic newest angiotensin and with low water solubility. This research investigates the interaction between ZOF and a β-cyclodextrin chemically modified derivative, 2-hydroxypropyl-β-cyclodextrin (HPBCD), in order to prove the formation of an inclusion complex with an enhanced water solubility profile of ZOF. In this research is reported for the first time the physicochemical characterization and the solubility profile of an inclusion complex between ZOF and HPBCD. Different spectroscopic techniques (UV absorption spectrometry, powder X-ray diffraction, attenuated total reflectance Fourier transform IR spectroscopy) were applied in order to prove the formation of the ZOF/HPBCD inclusion complex, both in water and in solid state, backed by thermal analysis (TGA/DTG/HF). The obtained results confirm that the physicochemical properties of the ZOF/HPBCD binary system, prepared using the kneading method, are different in comparison both with the parent substances and the corresponding physical mixture, thus suggesting that an inclusion complex was formed. After the formation of the inclusion complex with HPBCD, the solubility test indicated that the water solubility of ZOF was increased by 5 times.

Analyzing drug-drug interactions may unravel previously unknown drug action patterns, leading to the development of new drug discovery tools. We present a new approach to analyzing drug-drug interaction networks, based on clustering and topological community detection techniques that are specific to complex network science. Our methodology uncovers functional drug categories along with the intricate relationships between them. Using modularity-based and energy-model layout community detection algorithms, we link the network clusters to 9 relevant pharmacological properties. Out of the 1141 drugs from the DrugBank 4.1 database, our extensive literature survey and cross-checking with other databases such as Drugs.com, RxList, and DrugBank 4.3 confirm the predicted properties for 85% of the drugs. As such, we argue that network analysis offers a high-level grasp on a wide area of pharmacological aspects, indicating possible unaccounted interactions and missing pharmacological properties that can lead to drug repositioning for the 15% drugs which seem to be inconsistent with the predicted property. Also, by using network centralities, we can rank drugs according to their interaction potential for both simple and complex multi-pathology therapies. Moreover, our clustering approach can be extended for applications such as analyzing drug-target interactions or phenotyping patients in personalized medicine applications.

This research investigates the interaction between fosinopril sodium (FOS) and beta-cyclodextrin (β-CD) in aqueous solution and in solid state, in order to prove the formation of an inclusion complex between the two components. The stoichiometry of the inclusion complex was found as 1 : 1 by employing continuous variation method in UV. The formation constant was calculated as 278.93 M−1using Benesi-Hildebrand equation. The kneaded product (KP) and the physical mixture (PM) were further experimentally examined, using FTIR, powder X-ray diffractometry, and thermal analysis. The results confirm that the physicochemical properties of the FOS/β-CD KP are different from FOS and that the kneading method leads to formation of solid state inclusion complex between FOS andβ-CD. Structural studies of the FOS/β-CD were carried out using molecular modeling techniques, in order to explain the complexation mechanism and the host-guest geometry.