Influence of different techniques on formulation and comparative characterization of inclusion complexes of ASA with β-cyclodextrin and inclusion complexes of ASA with PMDA cross-linked β-cyclodextrin nanosponges

Acetyl salicylic acid (ASA), a non-steroidal anti-inflammatory drug, was formulated into inclusion complexes by grinding and precipitation with β-cyclodextrin and freeze drying with pyromellitic dianhydride (PMDA) cross-linked β-cyclodextrin nanosponges. Particle size, zeta potential, encapsulation efficiency, accelerated stability study, in vitro and in vivo release studies were used as characterization parameters. TEM studies showed that the particle sizes of different inclusion complexes of ASA have diameters ranging from 40.12?±?8.79 to 59.53?±?15.55?nm. It also revealed the regular spherical shape and sizes of complexes that are even unaffected after drug encapsulation. Zeta potential was sufficiently high to obtain a stable colloidal formulation. The in vitro and in vivo studies indicated a slow and prolonged ASA release from PMDA cross-linked β-cyclodextrin nanosponges over a long period. XRPD, DSC and FTIR studies confirmed the interactions of ASA with nanosponges. XRPD showed the crystalline nature of ASA decreased after encapsulation. These results indicate that ASA nanosponges formulation can be used for oral delivery.     

Cyclodextrin-based nanosponges of curcumin: formulation and physicochemical characterization

Curcumin is the source of the spice turmeric having potential application in tumor treatment but has limited therapeutic utility because of its poor aqueous solubility. Curcumin suppresses the onset of tumors as well as their growth and metastasis. Cyclodextrin-based nanosponges (NS) have been used to increase the solubility of curcumin and to control its release. The aim of the study was to formulate the complex of curcumin with β-cyclodextrin nanosponge obtained with dimethyl carbonate as a cross linker. The particle size of loaded nanosponge was found to be 487.3 nm with minimum polydispersibility index (0.476). The loaded NS have shown more solubilization efficiency (20.89 μg/ml) in comparison with plain curcumin (0.4 μg/ml) and β-CD complex (5.88 μg/ml). The zeta potential was sufficiently high (?27 mV) which indicates formation of a stable colloidal nanosuspension. The curcumin nanosponge complex (CrNS) was characterized for FTIR, XRD and DSC studies and it confirmed the interactions of curcumin with NS. The in vitro drug release of curcumin was controlled over a prolonged period of time. The in vitro hemolysis study showed that the complex was non-hemolytic. CrNS sample showed only a slight reduction in cytotoxicity against MCF-7 cells, which concludes that there is no change in molecular structure of curcumin in CrNS formulation.     

In vitro release modulation and conformational stabilization of a model protein using swellable polyamidoamine nanosponges of β-cyclodextrin

New swellable cyclodextrin-based poly(amidoamine) nanosponges, named PAA-NS10 and PAA-NS11, were synthesized by crosslinking β-cyclodextrin with either 2,2-bisacrylamidoacetic acid or with polyamidoamine segments deriving from 2,2-bisacrylamidoacetic acid and 2-methylpiperazine, respectively. Water uptake studies showed a tremendous swelling capacity of both nanosponges, forming hydrogels. Time dependent swelling experiments in various aqueous media showed that the nanosponge hydrogels were stable over a period of at least 72 h maintaining their integrity. Thermal analysis showed that the two nanosponges were stable up to 250 and 300 °C, respectively. Both PAA-NS10 and PAA-NS11 were converted to aqueous nanosuspensions using the High Pressure Homogenization technique. Bovine serum albumin (BSA) was used as model protein to study the encapsulating capacity of these new β-cyclodextrin-based PAA-nanosponges. High protein complexation capacity was observed, as confirmed by UV spectroscopy. BSA encapsulation efficiency was greater than 90% on w/w basis for both nanosponges. In vitro BSA release studies were carried out showing a prolonged release of albumin from the two swollen BSA loaded β-CD PAA-NS over a period of 24 h.     

Novel worm-like amphiphilic micelles of folate-targeted cyclodextrin/retinoic acid for delivery of doxorubicin in KG-1 cells

Folate-targeted cyclodextrin/retinoic acid (CD/RA) conjugate was synthesized using carbonyldiimidazole (CDI) and dimethylaminopyridine (DMAP). The structure of the produced macromolecule was studied by FTIR and ¹HNMR. The developed macromolecule could self-aggregate to form micelles. Critical micelle concentration (CMC) of the macromolecule was determined by pyrene as a fluorescent probe. Doxorubicin (DOX)-loaded micelles were prepared by direct dissolution method. To optimize the effect of cyclodextrin type (α or β), the molar ratio of RA to CD and the drug content, a full factorial design was used and their effects on particle size, polydispersity index, zeta potential, loading efficiency (LE%), and release efficiency (RE₂₄%) in 24 h were studied. Orientation of folate ligand on the surface of the micelles was studied by X-ray photoelectron spectroscopy (XPS) technique. The cytotoxicity of DOX-loaded micelles was studied on KG-1 cells which overexpressed folate receptor (FR) and FR-negative HepG2 cells using MTT assay. FTIR and ¹HNMR spectra confirmed successful production of the micelles and XPS spectra showed surface orientation of folate. The best results obtained from β-cyclodextrin with molar ratio of 4 to RA and 15 % drug content. The optimized micelles showed the particle size of 103?±?4 nm, zeta potential of ?36 mV, polydispersity index of 0.28?±?0.05, LE% of 100 %, and RE₂₄% of 69.88?±?1.6 %. The IC₅₀ of targeted micelles was half of non-targeted micelles and free DOX.     

Effect of preparation method on complexation of Cefdinir with β-cyclodextrin

The inclusion behaviour of β-cyclodextrin (βCD) was studied toward Cefdinir (CEF) in order to enhance the solubility and dissolution rate, following cyclodextrin complexation. Drug cyclodextrin solid systems were prepared by conventional methods of kneading (KN), co-evaporation (CE), spray drying (SD) and with a novel approach of microwave irradiation (MWI). The formation of inclusion complexes with βCD in the solid state, were confirmed by Differential scanning calorimetry (DSC), Fourier Transform Infrared spectroscopy (FTIR) and Scanning Electron Microscopy (SEM) studies, and comparative studies on the in vitro dissolution of CEF were carried out. Characterization of binary system by DSC, FTIR and SEM indicated that SD and MWI method resulted in formation of true complexes. Binary systems showed significant increase in dissolution rate as compared to plain drug. Amongst the binary systems MWI products were prepared in least time with better yield and highest dissolution rate.     

Inclusion complexes with cyclodextrin and usnic acid

Molecular inclusion complexes of usnic acid (UA) with β-cyclodextrin (β-CD) and 2-hydroxypropyl β-cyclodextrin (HP β-CD) were prepared by the co-precipitation method in the solid state in the molar ratio of 1:1. Structural complexes characterization was based on different methods, FTIR, ¹H NMR, XRD and DSC. Parallel to the complex by the above methods, corresponding physical mixtures of UA with cyclodextrins and complexing agents (β-CD, HP β-CD and UA) were analyzed. The results of DSC analysis showed that, at around 200 °C, the endothermal peak in the complexes with cyclodextrins originating from the UA melting has disappeared. Complex diffractogram patterns do not contain peaks characteristic for the pure UA. They are more appropriate to cyclodextrin diffractogram. This fact points to the molecular encapsulation of UA in the cyclodextrin cavity. Chemical shifts in ¹H NMR spectra after the inclusion of UA into the cyclodextrin cavity, especially H-3 protons (0.0012 and 0.0102 ppm in the β-CD and HP β-CD, respectively) and H-5 and H-6 (0.0134 ppm) and hydrogen from CH₃ (0.0073 ppm) HP β-CD also points to the formation of molecular inclusion complexes. The improved solubility of UA in water was achieved by molecular incapsulation. In the complex with β-CD the solubility is 0.3 mg/cm³, with HP β-CD 4.2 mg/cm³ while the uncomplexed UA solubility is 0.06 mg/cm³. The microbial activity of UA and both complexes was tested against eight bacteria and two fungi and during the test no reduced activity of UA in the complexes was observed.     

Preparation of gamma cyclodextrin stabilized solid lipid nanoparticles (SLNS) using stearic acid–γ-cyclodextrin inclusion complex

The inclusion complexation behaviour of higher chain fatty acid, stearic acid (SA) with gamma cyclodextrin has been investigated. The inclusion complex was characterized by FT-IR, ¹H NMR, 2D NMR, XRD and DSC techniques. The results showed that the SA molecule was entrapped inside the gamma cyclodextrin cavity. Further, inclusion complex was treated with lopinavir at 85 °C and emulsified with hot water at 85 °C. The resulted nanoemulsion was cooled down to form solid lipid nanoparticles (SLNs) stabilized with gamma cyclodextrin. Prepared SLNs were having average particle size of 212.5 ± 4.8 nm, zeta potential of ?19.7 ± 0.66 mV and drug loading of 57.54 ± 0.62 %. The surface characteristics of SLNs were also observed with transmission electron microscopy and atomic force microscopy. Results indicate that inclusion complex of SA and gamma cyclodextrin can be used for SLNs preparation.     

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.     

Enhancement of Dissolution Behavior of Aceclofenac by Complexation with β-Cyclodextrin-Choline Dichloride Coprecipitate

The objective of the present investigation was to study the effect of presence of choline dichloride (CDC) in β-cyclodextrin (β-CD) on in vitro dissolution of aceclofenac (AF) from molecular inclusion complexes. The molecular inclusion complexes of AF with β-CD coprecipitated with CDC in 1:1 and 1:2 M ratio were prepared using kneading method. In vitro dissolution of pure drug, physical mixtures, and cyclodextrin inclusion complexes (AF-β-CD-CDC) were carried out. Molecular inclusion complexes of aceclofenac with coprecipitated β-CD showed considerable increase in the dissolution rate in comparison with physical mixture and pure drug in 0.1 N HCl, pH 1.2 and phosphate buffer, pH, 7.4. Inclusion complexes with 1:2 M ratio showed maximum dissolution rate in comparison to other ratios. FTIR spectroscopy and differential scanning calorimetry studies indicated no interaction between AF and β-CD-CDC in complexes in solid state. Dissolution enhancement was attributed to the formation of water soluble inclusion complexes with the precipitated form of β-CD. The in vitro release from all the formulations was best described by first order kinetics (R ² = 0.9354 and 0.9268 in 0.1 N HCl and phosphate buffer, respectively) followed by Higuchi release model (R ² = 0.9029 and 0.9578 in 0.1 N HCl and phosphate buffer, respectively). In conclusion, dissolution of aceclofenac can be enhanced by using the β-CD-CDC coprecipitate as a host molecule.     

Preparation,optimization by 2<Superscript>3</Superscript> factorial design,characterization and in vitro release kinetics of lorazepam loaded PLGA nanoparticles

The aim of this work was to formulate the lorazepam loaded poly(lactic-co-glycolic) acid (PLGA) nanoparticles by optimization of different preparation variables using 2³ factorial design. The effect of three independent factors, the amount of polymer, concentration of the stabilizer and volume of organic solvent was investigated on two dependent responses, i.e., particle size and % drug entrapment efficiency. By using PLGA as polymer, PVA as a stabilizer and dimethyl sulfoxide as organic solvent lorazepam loaded PLGA nanoparticles were successfully developed through modified nanoprecipitation method. FTIR and DSC studies were carried out to examine the interaction between the excipients used and to explore the nature of the drug, the formulation and the nature of drug in the formulations. These nanoparticles were characterized for particle size, shape, zeta potential, % drug entrapment efficiency, % process yield and in vitro drug release behavior. In vitro evaluation showed particles size between 161.0 ± 5.4 and 231.9 ± 4.9 nm, % drug entrapment efficiency of formulations was in the range of 60.43 ± 5.8 to 75.40 ± 1.5, % process yield at 68.34 ± 2.3 to 81.55 ± 1.3 was achieved and in vitro drug release for these formulations was in the range of 49.2 to 54.6%. Different kinetics models, such as zero order, first order, Higuchi model, Hixson-Crowell model and Korsmeyer- Peppas model were used to analyze the in vitro drug release data. Preferred formulation showed particle size of 161.0 ± 5.4 nm, PDI as 0.367 ± 0.014,–25.2 mV zeta potential, drug entrapment efficiency as 64.58 ± 3.6% and 72.48 ± 2.5% process yield. TEM results showed that these nanoparticles were spherical in shape, and follow the Korsmeyer-Peppas model with a release exponent value of n = 0.658.     

Formulation and evaluation of gel containing nanostructured lipid carriers of tretinoin–Epi-β-CD binary complex for topical delivery

The objective of present research work was to formulate and evaluate topical gel containing tretinoin–cyclodextrin (CD) binary complex loaded into nanostructured lipid carriers (NLCs). Use of cyclodextrin and nanolipid carrier together in a system produced a synergistic effect by increasing the drug release and skin permeation, thus improving the overall therapeutic effect. Two different cyclodextrins i.e. β-CD and its water soluble polymeric derivative epichlorohydrin-β-cyclodextrin (EPI-β-CD) were used to obtain binary inclusion complex of drug-cyclodextrin (D-CD) systems by two different techniques (kneading and co-evaporation). The prepared solid complexes were characterized by FTIR, DSC, XRD etc. and the best system was selected for loading into nanolipid carriers. NLC comprising glyceryl mono stearate (GMS) and oleic acid were obtained by slightly modified emulsification evaporation method. Four different formulations of NLCs were suitability characterized for particle size, zeta potential, entrapment efficiency, drug loading and drug release. EPI-β-CD was found to be more effective than β-CD in enhancing solubility and dissolution properties of tretinoin. The most effective NLC formulation was incorporated into carbopol hydrogel which showed better permeation properties than that of the reference gel (0.1%).     

Effect of β-cyclodextrins based nanosponges on the solubility of lipophilic pharmacological active substances (repaglinide)

Cyclodextrin based nanosponges (CD-NS) are nanostructured cross-linked polymers, usually obtained by reacting cyclodextrin with a cross-linker such as carbonyldiimidazole, organic carbonates or (±) epichlorohydrin. They have been used to increase the solubility and stability of poorly soluble pharmacological active substances, as they combine the complex forming properties of CDs and properties of polymers (such as the high molecular weight). The affinity of CDs for certain lipophilic molecules is characteristic to the polymeric nano-structured system and allows the development of specific drug delivery systems. Knowing that cyclodextrin capacity to form inclusion complexes is maintained and enhanced when the CD molecules form aggregates, cross-link together or copolymerize with other compounds, we have synthesized cyclodextrin based nanosponges (from β-cyclodextrin and sulfobutylether-β-cyclodextrin). The complexing properties of the polymers were investigated against repaglinide (a hypoglycemic agent, practically insoluble in water). Solubility studies were performed according to the method reported by Higuchi and Connors and the phase solubility diagrams were plotted. The repaglinide-nanosponges complexes were prepared, lyophilized and the resulted inclusion complexes were characterized by FT-IR and NMR. The solubility profile and the loading capacity of the cyclodextrin based polymers were also determined.     

Preparation and characterization of cyclodextrin inclusion complex of naringenin and critical comparison with phospholipid complexation for improving solubility and dissolution

Naringenin, a flavonoid specific to citrus fruits shows a variety of therapeutic effects like anti-inflammatory, anticarcinogenic, and antitumour effects. But it is associated with some limitations like poor water solubility, poor dissolution, lower half-life, and rapid clearance from the body. With the aim of improving amorphous nature, water solubility, and dissolution profile of naringenin and its complexes were prepared with β-cyclodextrin in three different molar ratios (1:1, 1:2, and 1:3) by solvent evaporation method. These complexes were characterized for solubility, drug content, chemical interaction (using FTIR), phase transition behavior (using DSC), crystallinity (using XRPD), surface morphology (using SEM), and in vitro dissolution study. The results were also critically compared with the results obtained from naringenin-phospholipid complexes (from author’s previous study). The prepared complexes showed high drug content (ranging from 69.53 to 84.38 %) and about two fold improvement in water solubility (from 41.81 to 76.31 μg mL^?1 in the complex with 1:3 ratio). SEM of the complexes showed irregular and rough surface morphology. FTIR, DSC, and XRPD data confirmed the formation of the complex. Unlike the free naringenin which showed a total of only 48.78 % drug release at the end of 60 min, the complex showed 98.0–100 % in dissolution study. Thus it was concluded that the β-cyclodextrin of naringenin may be of potential use for improving bioavailability of poorly soluble phytoconstituents/herbal drugs. On critical comparison with the phospholipid complex of naringenin both the techniques were found almost equally effective in improving the solubility and the dissolution performance of naringenin in the complex form.     

Thermosensitive mucoadhesive gel formulation loaded with 5-Fu: cyclodextrin complex for HPV-induced cervical cancer

Human Papilloma Virus (HPV) infections are the major cause of cervical cancers. To achieve a better therapeutic efficacy and patient compliance in the treatment for HPV-induced cervical cancers, anticancer agent 5-fluorouracil has been formulated in a vaginal gel using the thermosensitive polymer Pluronic^® F127 together with alternative mucoadhesive polymers e.g., hyaluronic acid, Carbopol 934 and hydroxypropylmethylcellulose. To increase its aqueous solubility and to achieve the complete release of 5-FU from the gel, the drug was incorporated as its inclusion complex with 1:1 molar ratio with either β-cyclodextrin or hydroxypropyl-β-cyclodextrin. Following the characterization of drug:CD complexes, thermosensitive gel formulations containing different mucoadhesive polymers and the drug in free or complexed form were characterized in vitro by determining the gelation temperature and the rheological behavior of different formulations along with the in vitro release profiles of these formulations in pH 5.5 citrate buffer. It was observed that complexation with cyclodextrin accelerated the release of 5-FU with the exception of formulation containing Carbopol 934 as mucoadhesive polymer. As far as rheological properties are concerned, favorable thermosensitive in situ gelling properties were obtained with formulations containing HPMC as mucoadhesive polymer. Complete release of 5-FU from gels were obtained with both complexes of β-CD and HP-β-CD and cytotoxicity studies against HeLa human cervical carcinoma cells demonstrated that 1% 5-FU:CD complexes were equally effective as 1% free 5-FU indicating better therapeutic efficacy with lower dose.     

Ciprofloxacin Loaded Alginate/Chitosan and Solid Lipid Nanoparticles,Preparation, and Characterization

The aim of the present study was to develop controlled drug delivery systems based on nanotechnology. Two different nanocarriers were selected, chitosan-alginate nanoparticles as hydrophilic and solid lipid nanoparticles as lipophilic carriers. Nanoparticles were prepared and characterized by evaluating particle size, zeta potential, SEM pictures, DSC thermograms, percentage of drug loading efficiency, and drug release profile. The particle size of SLNs and Chi/Alg nanoparticles was 291 ± 5 and 520 ± 16. Drug loading efficiency of Chi/Alg and SLN particles were 68.98 ± 5.5% and 88 ± 4.5%. The drug release was sustained with chitosan-alginate system for about 45 hours whereas for SLNs >98% of the drug was released in 2 hours. Release profile did not change significantly after freeze drying of particles using cryoprotector. Results suggest that under in vitro condition chitosan/alginate systems can act as promising carriers for ciprofloxacin and may be used as an alternative system in sustained delivery of ciprofloxacin.     

Development and evaluation of orodispersible sustained release formulation of amisulpride–γ-cyclodextrin inclusion complex

Amisulpride (AMI) is an atypical antipsychotic having poor aqueous solubility and poor oral bioavailability. Inclusion complex between AMI and gamma cyclodextrin (γ-CD) was prepared by kneading method using 1:1 stoichiometry. Solubility of AMI was enhanced by 3.74 times after inclusion complex formation. Amisulpride–γ-cyclodextrin inclusion complex was characterized by FTIR, DSC and XRD techniques. Further sustained release granules of Amisulpride–γ-cyclodextrin inclusion complex (CDSR) were prepared by treating complex with molten stearic acid. Drug release from CDSR granules was sustained up to 12 h with 100 % stearic acid proportion. The integrity of AMI–γ-CD inclusion complex in lipid phase was assessed by XRD study. Finally orodispersible tablets of CDSR granules (OD-CDSR) were prepared using Ac-Di-Sol and microcrystalline cellulose. Disintegration time was assessed by both pharmacopoeial and modified method. Optimized formulation was rapidly disintegrated within 25 s. Thus solubility enhancement and sustained release of AMI was achieved by orodispersion of CDSR granules for improvement of patient compliance.     

Rapamycin-cyclodextrin complexation: improved solubility and dissolution rate

The objective of this study was to improve poor aqueous solubility and dissolution properties of anticancer drug rapamycin through formation of inclusion complexes with natural and modified cyclodextrins. Of the cyclodextrins tested, ??-cyclodextrin and hydroxypropyl-??-cyclodextrin did not complex with rapamycin. However, complexes of rapamycin with ??-cyclodextrin, methyl-??-cyclodextrin and hydroxypropyl-??-cyclodextrin were prepared and characterized by techniques such as Fourier Transform infrared spectroscopy, differential scanning calorimetry, phase solubility analysis and in vitro dissolution studies. According to the characterization data for the complexes, rapamycin water solubility was highly enhanced by all three ??-cyclodextrins with methyl-??-cyclodextrin complex resulting in particularly higher solubility enhancement. FTIR spectra and DSC thermograms supported the formation of inclusion complexes. The complexes showed highly improved dissolution rate in water. Complexation with cyclodextrin derivatives such as methyl-??-cyclodextrin and hydroxypropyl-??-cyclodextrin can provide promising alternatives for the formulation of rapamycin.     

Gel-sol evolution of cyclodextrin-based nanosponges: role of the macrocycle size

The effect of the macrocycle size on the gel-to-sol evolution of cyclodextrin-based hydrogel is here investigated by using Fourier transform infrared absorption in attenuated total reflectance geometry (FTIR-ATR). Different types of nanosponges obtained by polymerization of α- and β-cyclodextrin (CDNS) with an activated derivative of ethylenediaminetetraacetic acid have been progressively hydrated in order to follow the evolution of these systems from a gel state to a liquid suspension. The in deep analysis of the high-frequency vibrational dynamics of the hydrogel during its gel-sol evolution revealed that the microscopic origin of this phenomenon is strictly connected to different hydrogen bond environments in which water molecules confined in the pores of nanosponges can arrange. By following a well consolidated approach, the OH stretching band of water, clearly observed in the high-frequency range of the vibrational spectra of nanosponges hydrogel, has been decomposed into sub-bands assigned to different arrangements of water molecules at various degrees of cooperativity. A comparison of the diagrams obtained for homologous CDNS prepared from α- and β-CD shows how the size of cyclodextrin macrocycle allows to efficiently modulate the gelation points at constant cyclodextrin/crosslinker molar ratio n.     

A new controlled release system of chlorhexidine and chlorhexidine:βcd inclusion compounds based on porous silica

The purpose of this study was to prepare and characterize a controlled release system based on porous silica loaded with chlorhexidine (Cx) and its inclusion compounds in β-cyclodextrin (βcd), and to evaluate its antimicrobial activity. Acetate chlorhexidine (CxA), gluconate chlorhexidine (CxG), βcd:chlorhexidine acetate 2:1 (βcd:CxA) and βcd:chlorhexidine gluconate 2:1 (βcd:CxG) were incorporated into porous silica. Drug loading was characterized by FTIR, powder X-ray diffraction, thermal analysis and BET, and was shown to be in an amorphous state and porous matrix. The kinetics release parameter of the drug was established, which showed that the Cx systems release profile followed zero order release until 400 h and Higuchi model release until 750 h, after the burst effect at the first 8 h. Chlorhexidine therapeutic range was reached near first hour for all systems. The chlorhexidine porous silica system was biologically active against Enterococcus faecalis and Candida albicans in vitro. The systems showed an efficient Cx controlled release modulated by the presence of the β-cyclodextrin and by the porous silica matrices, providing effective antimicrobial activity.     

Inclusion complex formation of β-cyclodextrin and Naproxen: a study on exothermic complex formation by differential scanning calorimetry

Inclusion complex formation between β-cyclodextrin and Naproxen was investigated using differential scanning calorimetry (DSC) as a function of the β-cyclodextrin-to-Naproxen molar ratio, ranging from 0:5:1 to 5:1. When these mixtures are heated above the melting temperature of Naproxen, an exothermic peak is observed at a temperature slightly higher than the melting peak of Naproxen. This peak, which has not been previously reported, has been interpreted as an exothermic energy of inclusion complex formation. The magnitude of this complex formation peak was found to be dependent upon the composition of the β-cyclodextrin and Naproxen mixture and increased in magnitude to a maximum value at a β-cyclodextrin:Naproxen molar ratio of 2:1. In addition, Naproxen recrystallization and re-melting peaks seen in the cooling and re-heating scans, respectively, decreased in magnitude with increasing molar ratio and totally disappeared for the mixture with 5:1 of β-cyclodextrin to Naproxen ratio indicative of complete inclusion of Naproxen in the cyclodextrin cavities. Complete inclusion was further reflected by the disappearance of key Naproxen peaks in Fourier transform infrared spectra of samples recovered from DSC experiments. The large excess of β-cyclodextrin needed to fully complex the Naproxen was found to be due to slow kinetics. Increasing the hold time after the initial melting led to inclusion efficiencies up to 95 % even for the 2:1 mixture. These experiments suggest that ratios of β-cyclodextrin:Naproxen 2:1 or greater facilitate the process by increasing the presence of cyclodextrin molecules in the close proximity of the drug molecules and lead to high inclusion efficiencies.