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.     

Binary Systems of Nifedipine And Various Cyclodextrins in The Solid State. Thermal,FTIR, XRD studies

Nifedipine complexes with β-cyclodextrin (β-CD), γ-cyclodextrin (γ-CD), 2-hydroxypropyl-β-cyclodextrin (2HP-β-CD), randomly methylated-β-cyclodextrin (RM-β-CD) and heptakis(2,6-O-dimethyl)-β-cyclodextrin (DM-β-CD) have been prepared by both kneading and heating methods and their behaviour studied by differential scanning calorimetry (DSC), diffuse reflectance mid-infrared spectroscopy (FTIR) and X-ray diffractometry (XRD). DSC revealed the nifedipine melting endotherm with onset at approximately 171°C for the kneaded mixtures with β-CD, γ-CD and 2HP-β-CD, thus confirming the presence of nifedipine in the crystalline state, while some decrease in crystallinity was observed in the DM-β-CD kneaded mixture. With RM-β-CD, however, broadening and shifting of the nifedipine endotherm and reduction in its intensity suggested that the kneading could have produced an amorphous inclusion complex. These differing extents of interaction of nifedipine with the cyclodextrins were confirmed by FTIR and XRD studies. This revised version was published online in August 2006 with corrections to the Cover Date.     

Complexation of Ketoconazole by Native and Modified Cyclodextrins

Complexation of ketoconazole (KET), a broad-spectrum antifungal drug, with β- and γ-cyclodextrins (CDs), heptakis (2,6-di-O-methyl)-β-CD (2,6-DM-β-CD), heptakis (2,3,6-tri-O-methyl)-β-CD (TM-β-CD), 2-hydroxypropyl-β-CD (2HP-β-CD) and carboxymethyl-β-CD (CM-β-CD) was studied. The stability constants were determined by the solubility method at pH = 6 and for 2,6-DM-β-CD and CM-β-CD at pH = 5. At pH = 6, the stability constants increased in the order: TM-β-D < γ-CD < 2HP-β-CD < β-CD < CM-β-CD < 2,6-DM-β-CD. At pH = 5, due to the increased ionization of KET, the stability constant with CM-β-CD increased and with 2,6-DM-β-CD decreased. For complexes of KET with 2HP-β-CD and 2,6-DM-β-CD, the thermodynamic parameters of complexation were determined from the temperature dependence of the corresponding stability constants. For β–γ and TM-β-CD complexes, calculations using HyperChem 6 software by the Amber force field were carried out to gain some insight into the host–guest geometry.     

Spectrophotometric and thermoanalytical study of cypermethrin/cyclodextrin complexes

Cypermethrin/β-CD complexes were prepared at 1:2 cypermethrin/β-CD molar ratio by different complexation methods: conventional coprecipitation, suspension and kneading methods as well as “melting in solution” technique, which was developed in our laboratory. The complexes were investigated by UV-spectrophotometry and thermal analysis. It was found that complexes made by coprecipitation, suspension and kneading methods contained cypermethrin not only in complexed but also in uncomplexed form. The guest molecule in the complex prepared by “melting in solution” technique showed to be completely complexed, so it was the most effective complexation method studied.Investigating the solubility of cypermethrin with different cyclodextrins (CDs), it was established that the increase of solubility of cypermethrin was the highest in case of methylated cyclodextrins. The equilibrium constants were calculated from solubility isotherms. On the basis of these results, the heptakis(2,6-di-O-methyl)-β-cyclodextrin (DIMEB) complex was the more stable. By UV-irradiation measurements it was found that the photodegradation of cypermethrin was inhibited by methylated β-CDs.     

Synthesis of Mono-Amino Substituted γ-CD: Host–Guest Complexation and In Vitro Cytotoxicity Investigation

Cyclodextrins (CDs) are cyclic oligosaccharides which can trap hydrophobic molecules and improve their chemical, physical, and biological properties. γ-CD showed the highest aqueous solubility with the largest cavity diameter among other CD types. The current study describes a direct and easy method for nucleophilic mono-aminos to be substituted with γ-CD and tested for their ability to host the guest curcumin (CUR) as a hydrophobic drug model. The mass spectrometry and NMR analyses showed the successful synthesis of three amino-modified γ-CDs: mono-6-amino-6-deoxy-cyclodextrine (γ-CD-NH₂), mono-6-deoxy-6-ethanolamine-γ-cyclodextrine (γ-CD-NHCH₂CH₂OH), and mono-6-deoxy-6-aminoethylamino)-γ-cyclodextrin (γ-CD-NHCH₂CH₂NH₂). These three amino-modified γ-CDs were proven to be able to host CUR as native γ-CDs with formation constants equal to 6.70 ± 1.02, 5.85 ± 0.80, and 8.98 ± 0.90 mM⁻¹, respectively. Moreover, these amino-modified γ-CDs showed no significant toxicity against human dermal fibroblast cells. In conclusion, the current work describes a mono-substitution of amino-modified γ-CDs that can still host guests and showed low toxicity in human dermal fibroblasts cells. Therefore, the amino-modified γ-CDs can be used as a carrier host and be conjugated with a wide range of molecules for different biomedical applications, especially for active loading methods.     

Single Isomer N-Heterocyclic Cyclodextrin Derivatives as Chiral Selectors in Capillary Electrophoresis

In order to better understand the chiral recognition mechanisms of positively charged cyclodextrin (CD) derivatives, the synthesis, the pK_a determination by ¹H nuclear magnetic resonance (NMR)-pH titration and a comparative chiral capillary electrophoretic (CE) study were performed with two series of mono-substituted cationic single isomer CDs. The first series of selectors were mono-(6-N-pyrrolidine-6-deoxy)-β-CD (PYR-β-CD), mono-(6-N-piperidine-6-deoxy)-β-CD (PIP-β-CD), mono-(6-N-morpholine-6-deoxy)-β-CD (MO-β-CD) and mono-(6-N-piperazine-6-deoxy)-β-CD (PIPA-β-CD), carrying a pH-adjustable moiety at the narrower rim of the cavity, while the second set represented by their quaternarized, permanently cationic counterparts: mono-(6-N-(N-methyl-pyrrolidine)-6-deoxy)-β-CD (MePYR-β-CD), mono-(6-N-(N-methyl-piperidine)-6-deoxy)-β-CD (MePIP-β-CD), mono-(6-N-(N-methyl-morpholine)-6-deoxy)-β-CD (MeMO-β-CD) and mono-(6-N-(4,4-N,N-dimethyl-piperazine)-β-CD (diMePIPA-β-CD). Based on pH-dependent and selector concentration-dependent comparative studies of these single isomer N-heterocyclic CDs presented herein, it can be concluded that all CDs could successfully be applied as chiral selectors for the enantiodiscrimination of several negatively charged and zwitterionic model racemates. The substituent-dependent enantiomer migration order reversal of dansylated-valine using PIP-β-CD contrary to PYP-β-CD, MO-β-CD and PIPA-β-CD was also studied by ¹H- and 2D ROESY NMR experiments.     

Inclusion complexes of modified cyclodextrins with some flavonols

The inclusion complexes of four flavonols with modified cyclodextrins (CDs) have been investigated. The effect of heptakis (2,6-di-O-methyl) β-cyclodextrin (DM-β-CD) and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) on the aqueous solubility of flavonols, namely, galangin, kaempferol, quercetin, and myricetin was investigated, respectively. The increased solubility of all flavonols in the presence of CD was evidenced. The NMR experiment and molecular modeling studies showed that flavonols interact with each modified CD through different binding modes. Flavonols can complex with CDs largely by two binding modes. The first one is that B-ring of flavonols is oriented toward secondary rim of CD. The second one is that A-ring of flavonols is oriented toward secondary rim of CD. Whereas only the first mode was observed in DM-β-CD complexes, both the first and the second mode were observed in HP-β-CD complexes in this study.     

Cyclodextrins Initiated Ring-Opening Polymerization of Lactide Using 4-Dimethylaminopyridine (DMAP) as Catalyst: Study of DMAP/β-CD Inclusion Complex and Access to New Structures

Cyclodextrins (CDs) are cyclic oligosaccharides used in many fields. Grafting polymers onto CDs enables new structures and applications to be obtained. Polylactide (PLA) is a biobased, biocompatible aliphatic polyester that can be grafted onto CDs by -OH-initiated ring-opening polymerization. Using 4-dimethylaminopyridine (DMAP) as an organocatalyst, a quantitative functionalization is reached on native α-, β-, γ- and 2,3-dimethyl- β-cyclodextrins. Narrow molecular weight distributions are obtained with the native CDs (dispersity < 1.1). The DMAP/β-CD combination is used as a case study, and the formation of an inclusion complex (1/1) is shown for the first time in the literature, which is fully characterized by NMR. The inclusion of DMAP into the cavity occurs via the secondary rim of the β-CD and the association constant (K_a) is estimated to be 88.2 M⁻¹. Its use as an initiator for ring-opening polymerization leads to a partial functionalization efficiency, and thus a more hydrophilic β-CD-PLA conjugate than that obtained starting from native β-CD. Polymerization results including also the use of the adamantane/β-CD inclusion complex as an initiator suggest that inclusion of the DMAP catalyst into the CD may not occur during polymerization reactions. Rac-lactide does not form an inclusion complex with β-CD.     

Inclusion complexes of dihydroartemisinin with cyclodextrin and its derivatives: characterization,solubilization and inclusion mode

The characterization, inclusion complexation behavior and binding ability of the inclusion complexes of dihydroartemisinin with β-cyclodextrin and its derivatives, sulfobutyl ether β-cyclodextrin (SBE-β-CD), mono[6-(2-aminoethylamino)-6-deoxy]-β-cyclodextrin (en-β-CD) and mono{6-[2-(2-aminoethylamino)ethylamino]-6-deoxy}-β-cyclodextrin (dien-β-CD), were studied using phenolphthalein as a spectral probe. Spectral titration was performed in aqueous buffer solution (pH ca. 10.5) at 25 °C to determine the binding constants. The inclusion complexation behaviors were investigated in both solution and solid state by means of NMR, TG, XRD. The results showed that the water solubility and thermal stability of dihydroartemisinin were significantly increased in the inclusion complex with cyclodextrins (CDs). According to ¹H NMR and 2D NMR spectroscopy (ROESY), the A, B rings of dihydroartemisinin can be included into the cavity of CDs. The enhanced binding ability of CDs towards dihydroartemisinin was discussed from the viewpoint of the size/shape-fit concept and multiple recognition mechanism between host and guest.     

Preparation,Characterization, and Bioavailability of Host-Guest Inclusion Complex of Ginsenoside Re with Gamma-Cyclodextrin

This work aimed at improving the water solubility of Ginsenoside (G)-Re by forming an inclusion complex. The solubility parameters of G-Re in alpha (α), beta (β), and gamma (γ) cyclodextrin (CD) were investigated. The phase solubility profiles were all classified as AL-type that indicated the 1:1 stoichiometric relationship with the stability constants Ks which were 22 M⁻¹ (α-CD), 612 M⁻¹ (β-CD), and 14,410 M⁻¹ (γ-CD), respectively. Molecular docking studies confirmed the results of phase solubility with the binding energy of −4.7 (α-CD), −5.10 (β-CD), and −6.70 (γ-CD) kcal/mol, respectively. The inclusion complex (IC) of G-Re was prepared with γ-CD via the water-stirring method followed by freeze-drying. The successful preparation of IC was confirmed by powder X-ray diffraction (XRD), Fourier transform-infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). In-vivo absorption studies were carried out by LC-MS/MS. Dissolution rate of G-Re was increased 9.27 times after inclusion, and the peak blood concentration was 2.7-fold higher than that of pure G-Re powder. The relative bioavailability calculated from the ratio of Area under the curve AUC₀–_∞ of the inclusion to pure G-Re powder was 171%. This study offers the first report that describes G-Re’s inclusion into γ-CD, and explored the inclusion complex’s mechanism at the molecular level. The results indicated that the solubility could be significantly improved as well as the bioavailability, implying γ-CD was a very suitable inclusion host for complex preparation of G-Re.     

Use of cyclodextrins in isotachophoresis : VI. Cyclodextrins as leading electrolyte additives for the separation of bile acids

Cyclodextrins (CDs) and some of their methyl derivatives have been used for the optimization of the isotachophoretic separation of bile acids in aqueous electrolyte systems. The addition of heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin to the leading electrolyte proved useful for both the solubilization and the structural differentiation of the solutes studied and led to the successful separation of their mixtures. Other CDs tested, even if they gave a satisfactory solubilization effect, did not support the resolution of bile acid mixtures.     

Preparation, characterization and pharmacodynamic activity of supramolecular and colloidal systems of rosuvastatin–cyclodextrin complexes

In the present study influence of nature of selected cyclodextrins (CDs) and of methods of preparation of drug–CD complexes on the oral bioavailability, in vitro dissolution studies and pharmacodynamic activity of a sparingly water soluble drug rosuvastatin (RVS) was investigated. Phase solubility studies were conducted to find the interaction of RVS with β-CD and its derivatives, which indicated the formation of 1:1 stoichiometric inclusion complex. The apparent stability constant (K_1:1) calculated from phase solubility diagram were in the rank order of β-CD < hydroxypropyl-β-cyclodextrin (HP-β-CD) < randomly methylated-β-cyclodextrin (RM-β-CD). Equimolar drug–CD solid complexes prepared by different methods were characterized by the Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). FTIR study demonstrated the presence of intermolecular hydrogen bonds and ordering of the molecule between RVS and CDs in inclusion complexes. DSC and XRD analysis confirmed formation of inclusion complex by freeze dried method with HP-β-CD and RM-β-CD. Aqueous solubility and dissolution studies indicated improved dissolution rates of prepared complexes in comparison with drug alone. Moreover, CD complexes demonstrated of significant improvement in reducing total cholesterol and triglycerides levels as compared to pure drug. However the in vivo results only partially agreed with those obtained from phase solubility studies.     

Spectroscopic study and antioxidant activity of the inclusion complexes of cyclodextrins and amlodipine besylate drug

The aim of the study was to synthesize and characterization the inclusion complexes of amlodipine besylate (AML) drug with β-cyclodextrin (β-CD) and γ-cyclodextrin (γ-CD) which has antioxidating activity property. The guest/host interaction of AML with β-CD and γ-CD in order to complexation drug in β-CD and γ-CD were investigated. The interaction inclusion complexes was characterized by fourier transform infrared and ultraviolet–visible spectroscopies. The formation constant was calculated by using a modified Benesi–Hildebrand equation at 25 °C. The stoichiometry of inclusion complexes was found to be 1:1 for β-CD and γ-CD with AML drug. The antioxidant activity of AML drug and its inclusion complexes were determined by the scavenging of stable radical 2,2′-diphenyl-1-picrylhydrazyl (DPPH^·). Kinetic studies of DPPH^· with AML and CDs complexes were done. The experimental results confirmed the forming of AML complexes with CDs also these indicated that the AML/β-CD and AML/γ-CD inclusion complexes was the most reactive than its free form into antioxidant activity.     

Spectroscopic study and antioxidant properties of the inclusion complexes of rosmarinic acid with natural and derivative cyclodextrins

Measurement of total antioxidant activity/capacity of polyphenols in various solvent media necessitates the use of cyclodextrins to solubilize lipophilic antioxidants of poor aqueous solubility. The inclusion complexes of the slightly water soluble antioxidant, rosmarinic acid (RA), with α-cyclodextrin (α-CD), β-cyclodextrin (β-CD), 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), 2-hydroxyethyl-β-cyclodextrin (HE-β-CD), and methyl-β-cyclodextrin (M-β-CD) were investigated for the first time. The effect of cyclodextrins (CDs) on the spectral features of RA was measured in aqueous medium using UV-vis and steady-state fluorescence techniques by varying the concentrations of CDs. The molar stoichiometry of RA-CD inclusion complexes was verified as 1:1, and the formation constants of the complexes were determined from Benesi-Hildebrand equation using fluorescence spectroscopic data. Among the CDs, maximum inclusion ability was measured in the case of M-β-CD followed by HP-β-CD, HE-β-CD, β-CD and α-CD. Solid inclusion complexes were prepared by freeze drying, and their functional groups were analyzed by IR spectroscopy. Antioxidant capacity of CD-complexed rosmarinic acid was measured to be higher than that of the lone hydroxycinnamic acid by the CUPric Reducing Antioxidant Capacity (CUPRAC) method. The mechanism of the TAC increase was interpreted as the stabilization of the 1-e oxidized o-catechol moiety of RA by enhanced intramolecular H-bonding in a hydrophobic environment provided by CDs, mostly by M-β-CD.     

Study on inclusion complexes of meso-tetrakis(2-thienyl)porphyrin and Cu-meso-tetrakis(2-thienyl)porphyrin with cyclodextrins by spectroscopy method

In phosphate buffer solution of pH5.4, the interaction of meso-tetrakis(2-thienyl)porphyrin(H₂TTP) and Cu-meso-tetrakis(2-thienyl)porphyrin(Cu-TTP) with α-cyclodextrin(α-CD), β-CD, γ-CD, heptakis(2,3,6-tri-O-methyl)-β-CD(TM-β-CD) has been studied by means of UV-vis, fluorescence and ¹HNMR spectroscopy, respectively. The H₂TTP and Cu-TTP can form 1:2 inclusion complexes with TM-β-CD and 1:1 inclusion complexes with the other three cyclodextrins. In this paper, the inclusion constants (K) of H₂TTP and Cu-TTP for the formation of the inclusion complexes have been estimated from the changes of absorbance and fluorescence intensity in phosphate buffer solution. The inclusive capabilities of different kinds of cyclodextrins are compared. The result shows that the inclusion ability of α-CD with H₂TTP and Cu-TTP is the strongest among the three native CDs. The inclusion ability of modified β-CD with H₂TTP and Cu-TTP is stronger, compared to the native β-CD, which indicates that the capacity matching plays a crucial role in the inclusion procedure except for the hydrophobic effect. In addition ¹HNMR spectra supports the inclusion conformation of the TM-β-CD-Cu-TTP inclusion complex, indicating the interaction mechanism of inclusion processes.     

Changes in the reactivity of the fluorescent reagents carbazole-9-carbonyl chloride and 9-carbazolylacetic acid in the presence of cyclodextrins

Carbazole-9-carbonyl chloride (C9CC) and 9-carbazolylacetic acid (9CAA) were selected as model fluorescent reagents. The effect of different chemically modified cyclodextrins (CDs) added to the aqueous solutions of these reagents was studied in water and in buffered aqueous solutions at pH 4.5 and 8.8. The CDs employed were 2-hydroxypropyl-β-cyclodextrin (HP-βCD), 2,3-di-O-methyl-β-cyclodextrin (DM-βCD) and 2,3,6-tri-O-methyl-β-cyclodextrin (TM-βCD). The inclusion of these reagents inside the cavities of the CDs was verified and this process can affect the derivatization reaction because CDs can modify the reactivity of the guest molecules. The basic conditions necessary for the derivatization reaction between C9CC and amines lead to the formation of carbazole anion through hydrolysis followed by decarboxylation. In the presence of CDs, the hydrolysis-decarboxylation of carbazole-9-carbonyl chloride is faster than in buffered aqueous homogeneous solutions. The behaviour observed for these reagents in aqueous solutions of CDs was compared to the one observed in basic ethanolic solutions. These changes are particularly noticeable in the case of 2,3-di-O-methyl-β-CD and 2-hydroxypropyl-β-CD. The characteristics of the fluorescent reagents are compared to carbazole and 9-methylcarbazole as model compounds. This paper was presented at XIIIth International Cyclodextrin Symposium. Torino, Italy, May 14–17, 2006.     

Inclusion Compound of Efavirenz and γ-Cyclodextrin: Solid State Studies and Effect on Solubility

Efavirenz is an antiretroviral drug of widespread use in the management of infections with human immunodeficiency virus type 1 (HIV-1). Efavirenz is also used in paediatrics, but due to its very poor aqueous solubility the liquid formulations available resort to oil-based excipients. In this report we describe the interaction of γ-cyclodextrin with efavirenz in solution and in the solid state. In aqueous solution, the preferential host–guest stoichiometry was determined by the continuous variation method using ¹H NMR, which indicated a 3:2 host-to-guest proportion. Following, the solid inclusion compound was prepared at different stoichiometries by co-dissolution and freeze-drying. Solid-state characterisation of the products using FT-IR, ¹³C{¹H} CP-MAS NMR, thermogravimetry, and X-ray powder diffraction has confirmed that the 3:2 stoichiometry is the adequate starting condition to isolate a solid inclusion compound in the pure form. The effect of γ-cyclodextrin on the solubility of efavirenz is studied by the isotherm method.     

Hydrolysis and Enantiodiscrimination of (R)- and (S)-Oxazepam Hemisuccinate by Methylated β-Cyclodextrins: An NMR Investigation

Partially and exhaustively methylated β-cyclodextrins [(2-methyl)-β-CD (MCD), heptakis-(2,6-di-O-methyl)-β-CD (DIMEB), and heptakis-(2,3,6-tri-O-methyl)-β-CD (TRIMEB)] have been compared in the hydrolysis and enantiodiscrimination of benzodiazepine derivative (R)- or (S)-oxazepam hemisuccinate (OXEMIS), using nuclear magnetic resonance (NMR) spectroscopy as an investigation tool. After 6 h, MCD induced an 11% hydrolysis of OXEMIS, remarkably lower in comparison with underivatized β-CD (48%), whereas no hydrolysis was detected in the presence of DIMEB or TRIMEB after 24 h. DIMEB showed greater ability to differentiate OXEMIS enantiomers in comparison to TRIMEB, by contrast MCD did not produce any splitting of racemic OXEMIS resonances. Both enantiomers of OXEMIS underwent deep inclusion of their phenyl pendant into cyclodextrins cavities from their wider rims, but tighter complexes were formed by DIMEB with respect to TRIMEB.     

Comprehensive Characterisation of the Ketoprofen-β-Cyclodextrin Inclusion Complex Using X-ray Techniques and NMR Spectroscopy

Racemic ketoprofen (KP) and β-cyclodextrin (β-CD) powder samples from co-precipitation (1), evaporation (2), and heating-under-reflux (3) were analysed using X-ray techniques and nuclear magnetic resonance (NMR) spectroscopy. On the basis of NMR studies carried out in an aqueous solution, it was found that in the samples obtained by methods 1 and 2, there were large excesses of β-CD in relation to KP, 10 and 75 times, respectively, while the sample obtained by method 3 contained equimolar amounts of β-CD and KP. NMR results indicated that KP/β-CD inclusion complexes were formed and the estimated binding constants were approximately 2400 M⁻¹, showing that KP is quite strongly associated with β-CD. On the other hand, the X-ray single-crystal technique in the solid state revealed that the (S)-KP/β-CD inclusion complex with a stoichiometry of 2:2 was obtained as a result of heating-under-reflux, for which the crystal and molecular structure were examined. Among the methods used for the preparation of the KP/β-CD complex, only method 3 is suitable.     

Manufacturing and Assessing the New Orally Disintegrating Tablets,Containing Nimodipine-hydroxypropyl-β-cyclodextrin and Nimodipine-methyl-β-cyclodextrin Inclusion Complexes

The aim of the present study was to manufacture new orally disintegrating tablets containing nimodipine–hydroxypropyl-β-cyclodextrin and nimodipine–methyl-β-cyclodextrin inclusion complexes. For obtaining a better quality of the manufactured tablets, three methods of the preparation of inclusion complexes, in a 1:1 molar ratio, were used comparatively; namely, a solid-state kneading method and two liquid state coprecipitation and lyophilization techniques. The physical and chemical properties of the obtained inclusion complexes, as well as their physical mixtures, were investigated using Fourier transformed infrared spectroscopy, scanning electron microscopy, X-ray diffraction analyses, and differential scanning calorimetry. The results showed that the lyophilization method can be successfully used for a better complexation. Finally, the formulation and precompression studies for tablets for oral dispersion, containing Nim–HP-β-CD and Nim–Me-β-CD inclusion complexes, were successfully assessed.