The aim of this study was to investigate the use of inclusion complexation technique employing β-cyclodextrin in improving the dissolution profile of candesartan cilexetil, a BCS class-II drug, and to formulate the inclusion complex into orodispersible tablets. The inclusion complexes were formed by physical mixing, kneading, coevaporation, and lyophilisation methods. Inclusion complexes were characterized by FTIR, DSC, XRD, NMR, and mass spectral studies. Inclusion complexes prepared using kneading, and lyophilisation techniques in the molar ratio 1 : 5 with β-cyclodextrin were used for formulating orodispersible tablets by direct compression with different superdisintegrants like croscarmellose sodium, crospovidone, sodium starch glycolate, and low substituted hydroxypropyl cellulose in varying concentrations. The directly compressible powder was evaluated for precompression parameters, and the prepared orodispersible tablets were evaluated for postcompression parameters. Drug-excipient compatibility studies showed no interaction, and characterization proved the formation of inclusion complex. In vitro disintegration time was found to be within 3 minutes, and all the formulations showed complete drug release of 100% within 20 minutes. The optimized formulation was found to be stable after 6 months and showed no significant change in drug content. This work proved β-cyclodextrins to be effective solubilizing agent in improving the solubility of poorly water soluble drugs.

The purpose of our study was to improve the solubility, bioavailability, and efficacy of zotepine (ZTP) by brain-targeted intranasal delivery of microemulsion (ME) and its physicochemical properties, the pharmacokinetic and pharmacodynamic parameters were evaluated. The optimized ME formulations contain 10% w/w of oil (Capmul MCM C8, monoglycerides, and diglycerides of caprylic acid), 50% w/w of Smix (Labrasol and Transcutol HP, and 40% w/w of water resulting in a globule size of 124.6 ±3.52 nm with low polydispersity index (PDI) (0.212 ± 0.013) and 2.8-fold higher permeation coefficient through porcine nasal mucosa compared to pure drug. In vitro cell line studies on RPMI 2650, Beas-2B, and Neuro-2A revealed ZTP-ME as safe. ZTP-ME administered intranasally showed higher AUC0-t24 (18.63 ± 1.33 h x µg/g) in the brain by approximately 4.3-fold than oral ME (4.30 ± 0.92 h × µg/g) and 7.7-fold than intravenous drug solutions (2.40 ± 0.36 h × µg/g). In vivo anti-schizophrenic activity was conducted using catalepsy test scores, the formulation showed better efficacy via the intranasal route; furthermore, there was no inflammation or hemorrhage in the nasal cavity. The results concluded that the ZTP microemulsion as a safe and effective strategy could greatly enhance brain distribution by intranasal administration.

Naringenin (NRG) is a flavonoid and has been reported as an anti-osteoporotic agent. However, poor bioavailability may limit the anti-osteoporotic potential of the drug. The purpose of the study was to compare the anti-osteoporotic activity of naringenin nanosuspension (NRG-NS) with the NRG and standard therapeutic drug, raloxifene hydrochloride (RLX). Here, NRG-NS showed anti-osteoporotic activity in MG-63 cells by upregulating the osteocalcin levels. The in vivo anti-osteoporotic activity of NRG-NS was further investigated in an osteoporotic rat model to mimic the post-menopausal condition. The animals were randomized and separated into six groups. The animals were treated with RLX (p.o., 5.4 mg/kg), NRG (p.o., 20 mg/kg), NRG-NS (p.o., 20 mg/kg), and blank-NS for 60 days after completion of a 30-day post-surgery period and compared with control and ovariectomized (OVX) groups. After the treatment, body and uterine weights, biochemical estimation in serum (calcium, phosphorus, acid phosphatase, alkaline phosphatase, osteocalcin), bone parameters (length, diameter, dry weight, density, ash weight, bone mineral content) and bone microarchitecture by histopathology were determined. The results showed the protective effects of NRG-NS on osteoblast-like MG-63 cells. The biochemical estimations confirmed the normalization of parameters viz., alkaline phosphatase, calcium concentrations, and bone density with a decrease in levels of acid phosphatase and inorganic phosphorus with NRG-NS as compared to plain NRG. The results indicated that the oral administration of NRG-NS could be a potential therapeutic formulation for the treatment of osteoporosis.

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In the present research, an attempt was made to study enhancement of solubility and bioavailability of azithromycin, a sparingly water soluble macrolide antibiotic, by use of inclusion complexation technique, using 1:1 and 1:2 w/w ratios of three complexing agents-β-cyclodextrin, epichlorohydrin-βcyclodextrin and sulfobutylether cyclodextrin. Two methods were used-solvent evaporation and freeze drying/lyophilisation. Drug-excipients incompatibilities were studied using Fourier transform Infra-red spectroscopy and Differential scanning calorimetry. IR spectra did not show any significant changes in characteristic peaks of pure drug and excipients. DSC thermograms showed characteristic endothermic peaks at respective melting points of pure drug and excipients, thus ruling out of any undesirable interactions. Drug content of all prepared 12 inclusion complexes ranged from 97.4-99.5 %. Prepared inclusion complexes were characterised using In-Vitro dissolution studies, kinetic modelling patterns, Scanning electron microscopy images and X Ray Diffractograms. In Vitro drug profiles showed 96 % drug release for inclusion complexes using Sulfobutyl ether βcyclodextrin, prepared using freeze drying method. From the kinetics, it could be possibly stated that the release from the matrix was through diffusion. The XRD pattern depicted by optimised complexes reveals a decrease in the number of 2θ peaks which probably represents decrease in crystallinity. SEM images also showed the nature of particles to be highly porous. Thus, it can be concluded that, Inclusion complexation technique using freeze drying method, and newer derivatives of β-cyclodextrin as complexing agents has proven to be highly effective in improving bioavailability of poorly water-soluble drugs than β-Cyclodextrin alone.