A new drug nanocarrier consisting of chitosan and hydoxypropylcyclodextrin.

The objective of the present work was to develop a new drug nanocarrier consisting of nanoparticles made of chitosan and cyclodextrins. The rationale behind the design of this new nanosystem was to simultaneously implement the cyclodextrin drug complexation power and the inherent properties of chitosan nanoparticles, in a unique delivery system. The complexation with the cyclodextrin permits the solubilization as well as the protection for sensitive drugs, whereas the entrapment in the chitosan network is expected to facilitate their absorption. Chitosan nanoparticles including hydroxypropylcyclodextrins could be prepared by the ionic crosslinking of chitosan with sodium tripolyphosphate in the presence of cyclodextrins. Two hydrophobic drugs, triclosan and furosemide, were selected as models for complexation with the cyclodextrin and further entrapment in the chitosan nanocarrier. The resulting nanosystems were thoroughly characterized for their size and zeta potential and also for their ability to associate and deliver the complexed drugs. The results showed that the size of the nanoparticles was slightly affected by the incorporation of cyclodextrins, whereas the zeta potential did not suffer a significant modification. Moreover, the complexation of the drugs with the cyclodextrin facilitated their entrapment into the nanoparticles, increasing up to 4 and 10 times (for triclosan and furosemide, respectively) the final drug loading of the nanoparticles. These results led to the conclusion that the drug-cyclodextrin complex was efficiently retained in the nanoparticulate structure. Finally, the in vitro release profile observed for these nanoparticles was characterized by an initial fast release followed by a delayed release phase. In conclusion, this new nanosystem offers an interesting potential for the transmucosal delivery of hydrophobic compounds.     

Cyclodextrins as solubilizers: Formation of complex aggregates

Three different techniques were applied to investigate aggregation of drug/cyclodextrin complexes, that is, drug permeation through semi-permeable membranes, determination of changes in the value of activity coefficients of drug/cyclodextrin complex solutions and transmission electron microscopy (TEM). The aqueous solutions studied contained γ-cyclodextrin, 2-hydroxypropyl-γ-cyclodextrin or mixtures thereof, and hydrocortisone, amphotericin B, diclofenac sodium or indomethacin. The permeation studies indicated that drug/cyclodextrin complex monomers (i.e., unaggregated complexes) were dominating at cyclodextrin concentrations below 5% (w/v). Then formation of aggregates gradually increased with increasing cyclodextrin concentration until all increase in dissolved drug/cyclodextrin complexes was due to formation of cyclodextrin aggregates. This happened even though the observed phase-solubility diagrams were linear, that is, were of A_L-type. The activity coefficients showed positive deviation from ideal state. This positive deviation is due to concurrent of several processes, that is, hydration, aggregation and complex formation. The observed deviations from ideality indicated that complex aggregates were formed in the aqueous complexation media. TEM pictures showed formation of aggregates in both pure aqueous cyclodextrin solutions as well as in cyclodextrin solutions that had been saturated with hydrocortisone. The aggregate diameter was between 10 and 100 nm but larger aggregates with diameter of about 200 nm were formed through assemble of smaller aggregates. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:719–729, 2010     

Chitosan microspheres with hydrocortisone and hydrocortisone–hydroxypropyl-β-cyclodextrin inclusion complex

In the present study, an inclusion complex composed of hydrocortisone acetate (HC) and hydroxypropyl-β-cyclodextrin (HPβCD) was prepared by the spray-drying method. HC alone, HC inclusion complex or HC with HPβCD as a physical mixture were incorporated into chitosan microspheres by spray-drying. The inclusion complex and microspheres were characterized by X-ray powder diffractometry and differential scanning calorimetry (DSC). Microspheres were studied with respect to particle size distribution, drug content and in vitro drug release. The results indicate that the HCHPβCD inclusion complex is more water soluble than HC alone. The HC release rates from chitosan microspheres were influenced by the drug/polymer ratio in the manner that an increase in the release rate was observed when the drug loading was decreased. However, release data from all samples showed significant improvement of the dissolution rate for HC, with 25–40% of the drug being released in the first hour compared with about 5% for pure HC. The complexation method and microsphere preparation method (spray-drying) is simple with great potential for industrial production.     

Influence of cyclodextrins and chitosan, separately or in combination, on glyburide solubility and permeability.

The effect of chitosan and of different concentrations of beta- or hydroxypropyl-beta-cyclodextrins, separately or in various (w/w) combinations, on the dissolution characteristics of glyburide (an oral hypoglycemic agent subject to incomplete and variable bioavailability) and on its permeability through Caco-2 cells has been investigated. Cyclodextrins (and particularly the hydroxypropyl-derivative, in virtue of its higher water solubility) were clearly more effective than chitosan in enhancing the drug dissolution properties: the aqueous glyburide solubility was improved 40-fold in the presence of 25 mM hydroxypropyl-beta-cyclodextrin, 25-fold in the presence of 13 mM beta-cyclodextrin (saturation solubility) and only 3-fold in the presence of chitosan at its saturation concentration (0.5% w/v). When chitosan and cyclodextrin were simultaneously present, a strong reduction of the cyclodextrin solubilizing efficiency towards the drug was observed, and it was attributed to a possible competition effect of polymer and glyburide for the interaction with the macrocycle. By contrast, permeation studies revealed that chitosan was more powerful than cyclodextrins in enhancing the glyburide permeability through Caco-2 cells. This was probably in virtue of the polymer's favourable effect on the tight junctions opening, as demonstrated by the significant decrease in the transepithelial electrical resistance recorded in its presence. Moreover, interestingly, when using the carriers together, conversely from solubility studies, a significant (P < 0.05) synergistic effect in enhancing glyburide apparent permeability was revealed in permeation experiments.     

Complexation of the interferon inducer, bropirimine, with hydroxypropyl-β-cyclodextrin

Bropirimine (ABPP) is an orally active immunomodulator that increases endogenous alpha-interferon and other cytokines used clinically against carcinoma in situ of the bladder. The oral absorption of ABPP is poor because its low solubility in water. The purpose of this study is to develop a technological procedure useful to increase the water solubility of ABPP. To this end, the interaction of ABPP with several cyclodextrin derivatives--, β-, γ- and hydroxypropyl-β-cyclodextrin with a degree of substitution 2.7 (HPβCD) was studied and the effect of the complexation process on the water solubility of the drug was evaluated. The best results were obtained with the hydroxypropyl derivative, HPβCD, that interacts in a 1:1 drug:cyclodextrin molar ratio. The inclusion complex ABPP–HPβCD was characterized in solution by nuclear magnetic resonance (¹H-NMR). The solid inclusion complex was obtained by freeze-drying and characterized by differential scanning calorimetry (DSC), X-ray diffractometry and mass spectrometry. The dissolution rate of ABPP from the HPβCD solid inclusion complex was increased compared to the powdered drug but not differences were found between the complex and a physical mixture with a similar molar ratio. The increase of the dissolution rate of the drug can be attributed to the breakdown in solution of the drug dimers in the presence of the cyclodextrin and to the complex formation.     

Drug permeation through biomembranes: cyclodextrins and the unstirred water layer

Surface of the living epithelia is covered with mucus, a gel-like fluid containing mainly water (90-98%) and mucin (2-5%). This aqueous gel-like matrix forms an unstirred water layer (UWL) creating an aqueous diffusion barrier that hampers drug permeation through mucosal barriers. Frequently, the UWL is the main drug permeation barrier, especially in the case of small-molecular-weight lipophilic drugs. Under such conditions drug permeation can often be enhanced by forming water-soluble drug/cyclodextrin complexes. Cyclodextrins enhance drug delivery through biomembranes by increasing drug permeation through the UWL, that is, by increasing the availability of dissolved drug molecules juxtaposed to the membrane surface. Cyclodextrins only enhance drug permeation when the UWL contributes to the permeation barrier. Cyclodextrins do not enhance drug permeation when the permeation resistance of the UWL is much less than that of the membrane itself. The effect depends also on the physicochemical properties of the drug. As a rule the best results are obtained for lipophilic drugs that are poorly soluble in water, that form water-soluble complexes with cyclodextrins and that possess, as dissolved drug molecules, relatively high permeability through lipophilic biomembranes. It is extremely important to optimize drug vehicles with regard to the amount of cyclodextrin. Too much or too little cyclodextrin will lead to less than optimal drug availability. Good understanding of cyclodextrin complexation and how cyclodextrin affect drug permeation through biomembranes is essential for successful development of cyclodextrin-containing drug formulations.     

Influence of hydroxypropyl-beta-cyclodextrin complexation on piroxicam release from buccoadhesive tablets.

Interaction of piroxicam (PX) and hydroxypropyl-beta-cyclodextrin (HPbetaCD) was investigated in solution and in the solid state. Solubility studies demonstrated the formation of the PX-HPbetaCD inclusion complex with 1:1 stoichiometry. Equimolecular PX-HPbetaCD solid systems were prepared and characterized by differential scanning calorimetry, Fourier transform infrared spectroscopy, and X-ray diffractometry. Modification of the release of a sparingly water-soluble drug, PX, from hydrophilic matrices using cyclodextrin complexation was evaluated. The buccoadhesive controlled release tablets for the delivery of PX were prepared by direct compression of hydroxypropylmethyl cellulose (HPMC) and Carbopol 940 (C940), which showed superior bioadhesion properties compared to HPMC. The tablets were evaluated for their dissolution, swelling and mucoadhesive properties. The in vitro release results demonstrated that matrix tablets containing the PX-HPbetaCD solid complex displayed faster PX release compared to those containing a physical mixture or "free" drug. Differences in release rates of PX from the tablets could be attributed to the presence of the polymers and to cyclodextrin complexation. The effect of the polymers on PX release can affect the drug solubility (complexation) and polymer water uptake (swelling). Higher polymer water uptake may result in higher drug solubility and diffusivity in a hydrated polymeric environment. Drug complexation affected also its diffusivity through the semipermeable membrane.     

Inclusion complexation of glibenclamide with 2-hydroxypropyl-β-cyclodextrin in solution and in solid state

Phase solubility diagrams have been used to investigate complexation between 2-hydroxypropyl-β-cyclodextrin (HPBCD) and glibenclamide (GM) in aqueous medium. More stable GM-HPBCD complexes were formed in alkaline medium (in which the drug is in ionized form) than in acid medium (in which the drug is in non-ionized form). The formation of solid GM-HPBCD inclusion complexes has been evaluated by using kneading, spray-drying and freeze-drying methods. Characterization of the resulting mixtures by X-ray diffraction, infrared spectroscopy and differential scanning calorimetry indicated that inclusion complexes can be obtained by spray drying and freeze drying but not by kneading. According to the phase solubility results, drug solubility in alkaline medium was greatly improved by inclusion with HPBCD, whereas in acid medium inclusion with HPBCD had no appreciable effect. Cyclodextrin complexation of ionized drug molecules in alkaline medium resulted in greater total solubilization, i.e., solubilization of the drug due to both cyclodextrin complexation and ionization.     

Competitive displacement of drugs from cyclodextrin inclusion complex by polypseudorotaxane formation with poloxamer: implications in drug solubilization and delivery

The competitive interactions between the poly-[propylene oxide] (POO)-poly-[ethylene oxide] (PEO) block copolymer poloxamer 407 (Pluronic F127) and two drugs, triamcinolone acetonide and ciclopirox olamine, by the formation of inclusion complexes with two cyclodextrin hydrophilic derivatives, hydroxypropyl-β-cyclodextrin (HPβCD; molar substitution (MS) 0.65) and partially methylated-β-cyclodextrin (MβCD; MS 0.57), were studied by means of one-dimensional (1)H NMR, 2D ROESY experiments, solubility studies and drug release studies. 1D and 2D NMR and solubility studies indicate that both triamcinolone acetonide and ciclopirox olamine form stable inclusion complexes with the cyclodextrin derivatives. In the case of ciclopirox olamine the complex was more stable at pH 1. Effective complexation of poloxamer with the two cyclodextrins (CDs) was also evidenced by NMR analysis, and competitive displacement of the drugs from the CD cavity by the polymer was observed. Drug solubility in CD solutions was not modified by the addition of polymers, indicating that a decrease in solubility due to the competitive displacement is probably compensated by the solubilizing effect of polymer micellization. Finally, polypseudorotaxanes formation has a significant influence on the release of the drugs studied. Changes in the release rate depend on the stability of drug-CD inclusion complex and on cyclodextrin concentration in the bulk solution; so polypseudorotaxane formation can be employed to modulate drug controlled release from thermosensitive hydrogels.     

A Study on Improvement of Solubility of Rofecoxib and its effect on Permeation of Drug from Topical Formulations

Rofecoxib, a practically insoluble cox-2 selective nonsteroidal antiinflammatory agent was subjected to improvement in solubility by preparing its binary mixtures with β cyclodextrin using various methods such as physical mixing, co-grinding, kneading with aqueous methanol and co-evaporation from methanol-water mixture. Characterization of the resulting binary mixtures by differential scanning calorimetry and X-ray diffraction studies indicated partial amorphization of the drug in its binary mixtures. In vitro dissolution studies exhibited remarkable increase in rate and extent of dissolution of the drug from its complexes with β -cyclodextrin. Pure rofecoxib as well as its co-ground binary mixture were formulated as aqueous gels for topical application. In vitro skin permeation of rofecoxib from formulation containing rofecoxib-cyclodextrin complex was significantly higher (p<0.05) at 1, 2, 12, 18 and 24 hr as compared to formulation containing pure rofecoxib. This could be attributed to better solubility of binary mixture in the aqueous gel vehicle leading to greater concentration gradient between the vehicle and skin and hence higher flux of the drug.     

Ionotropically Gelled Novel Hydrogel Beads: Preparation, Characterization and In vitro Evaluation

Prolonged release drug delivery system of stavudine was made by ionotropic gelation and polyelectrolyte complexation technique. Cross-linking reinforced chitosan-gellan complex beads were prepared by gelation of anionic gellan gum, the primary polymer, with oppositely charged counter ion to form beads which were further complexed with chitosan as a polyelectrolyte. The effect of this polymer on release profile of drug was studied. Beads without chitosan complexation were also made. The reaction of chitosan-gellan complex dominates the formation of skin layer on the surface of beads. Stavudine an antiretroviral drug was selected as novel drug for the experiment. The final formulations were subjected to in vitro evaluation and several characterization studies. Batches with gellan gum shows Higuchi model, while chitosan-gellan shows zero order release. All the batches with copolymer showed sustained the drug release more than 12 h, whereas with gellan gum alone showed up to 10 h. Batches with chitosan showed maximum drug encapsulation efficiency.     

β-cyclodextrin complexes of celecoxib: Molecular-modeling, characterization, and dissolution studies

Celecoxib, a specific inhibitor of cycloxygenase-2 (COX-2) is a poorly water-soluble nonsteroidal anti-inflammatory drug with relatively low bioavailability. The effect of beta-cyclodextrin on the aqueous solubility and dissolution rate of celecoxib was investigated. The possibility of molecular arrangement of inclusion complexes of celecoxib and beta-cyclodextrin were studied using molecular modeling and structural designing. The results offer a better correlation in terms of orientation of celecoxib inside the cyclodextrin cavity. Phase-solubility profile indicated that the solubility of celecoxib was significantly increased in the presence of beta-cyclodextrin and was classified as AL-type, indicating the 1:1 stoichiometric inclusion complexes. Solid complexes prepared by freeze drying, evaporation, and kneading methods were characterized using differential scanning calorimetry, powder x-ray diffractometry, and scanning electron microscopy. In vitro studies showed that the solubility and dissolution rate of celecoxib were significantly improved by complexation with beta-cyclodextrin with respect to the drug alone. In contrast, freeze-dried complexes showed higher dissolution rate than the other complexes.     

Enhancing and sustaining the topical ocular delivery of fluconazole using chitosan solution and poloxamer/chitosan in situ forming gel

Fungal keratitis is a serious disease that can lead to loss of vision. Unfortunately, current therapeutic options often result in poor bioavailability of antifungal agents due to protective mechanisms of the eye. The aim of this work was to evaluate the potential of a chitosan solution as well as an in situ gel-forming system comprised of poloxamer/chitosan as vehicles for enhanced corneal permeation and sustained release of fluconazole (FLU). For this, in vitro release and ex vivo corneal permeation experiments were carried out as a function of chitosan concentration from formulation containing the chitosan alone and combined with the thermosensitive polymer, poloxamer. Microdialysis was employed in a rabbit model to evaluate the in vivo performance of the formulations. The in vitro release studies showed the sustained release of FLU from the poloxamer/chitosan formulation. Ex vivo permeation studies across porcine cornea demonstrated that the formulations studied have a permeation-enhancing effect that is independent of chitosan concentration in the range from 0.5 to 1.5% w/w. The chitosan solutions alone showed the greatest ex vivo drug permeation; however, the poloxamer/chitosan formulation presented similar in vivo performance than the chitosan solution at 1.0%; both formulations showed sustained release and about 3.5-fold greater total amount of FLU permeated when compared to simple aqueous solutions of the drug. In conclusion, it was demonstrated that both the in situ gelling formulation evaluated and the chitosan solution are viable alternatives to enhance ocular bioavailability in the treatment of fungal keratitis.     

Effect of preparation technique on the properties of liposomes encapsulating ketoprofen-cyclodextrin complexes aimed for transdermal delivery

The combined approach of cyclodextrin complexation and entrapment in liposomes was investigated in order to develop an effective topical formulation of ketoprofen. Equimolar complex of drug and hydroxypropyl-beta-cyclodextrin (HPbetaCyd) was added at different concentrations to the aqueous phase of liposomes consisting of phosphatidylcholine and cholesterol (60%/40%, w/w). Liposomes were prepared with different techniques, such as thin layer evaporation, freezing and thawing, extrusion through microporous membrane, and reverse phase evaporation method, obtaining, respectively, multi-lamellar vesicles (MLV), frozen and thawed MLV (FATMLV), small uni-lamellar vesicles (SUV) and large uni-lamellar vesicles (LUV). Size and morphology of the different types of liposomes were investigated by light scattering analysis, transmission electron microscopy, and confocal laser scanning microscopy, whereas drug entrapment efficiency was determined by dialysis experiments. Cyclodextrin complexation improved drug solubilization and allowed a strong improvement of its entrapment into the aqueous liposomal phase. Liposome preparation method and operating conditions clearly affected both liposome size and drug loading capacity. Encapsulation efficiency increased with increasing the complex concentration up to 10 mM, and was in the order MLV>LUV>SUV. An opposite behaviour was observed for FATMLV, probably due to the freezing phase required by such a preparation method, which reduced the complex solubility. Moreover, it was not possible to use higher complex concentrations, due to the destabilizing effect of cyclodextrins toward the liposomal membrane. Permeability studies of drug-HPbetaCyd complexes, directly in solution or incorporated in liposomes, performed across artificial membranes simulating the skin behaviour, highlighted, as expected, a prolonged release effect of liposomal formulations. Furthermore, the drug permeation rate depended on the vesicle characteristics and varied in the order: SUV>MLV=FATMLV>LUV. Therefore, the most suitable liposome preparation method can be suitably selected on the basis of drug encapsulation efficiency and/or desired drug release rate.     

Elastic liposomes bearing meloxicam-beta-cyclodextrin for transdermal delivery

The ultra-flexible lipid vesicles, the elastic liposomes bearing meloxicam-beta-cyclodextrin complex were prepared for its topical administration with the aim of simultaneously exploiting the favorable properties of both the carriers. The prepared meloxicam-beta-cyclodextrin complex was evaluated using DSC, XRD and FT-IR, which indicates the formation of inclusion complex in a molar ratio of 1:2 of meloxicam and beta-cyclodextrin (beta-CD). The elastic liposomes were prepared by conventional rotary evaporation method and characterized for various parameters such as vesicle shape and surface morphology, size and size distribution, entrapment efficiency, elasticity, stability and in-vitro release pattern. Permeability studies of meloxicam and meloxicam-beta-cyclodextrin complex, as such or incorporated in elastic liposomes performed both across artificial membranes and rat skin highlighted a favorable effect of cyclodextrin on drug permeation rate, due to its solubilizing action. Moreover skin-permeation enhancer property of elastic liposomes has been evidenced. Skin permeation potential of the developed formulation was assessed using confocal laser scanning microscopy (CLSM), which revealed an enhanced permeation of the formulation to the deeper layers of the skin (up to 160 microm) following channel like pathways. Skin permeation profile of elastic liposomal formulation bearing meloxicam-beta-cyclodextrin complex was observed and the investigations revealed an enhanced transdermal flux (12.48+/-0.9 microg/cm(2)/h) and decreased lag time (0.7 h) for meloxicam. The obtained flux was nearly 1.4 and 9.1 times higher than elastic liposomal formulation bearing meloxicam and plain drug solution, respectively (P<0.005). The results indicate that the elastic liposomes may be promising vehicles for the transdermal delivery of meloxicam.     

In vitro evaluation of natural and methylated cyclodextrins as buccal permeation enhancing system for omeprazole delivery

In this work the enhancing effect of cyclodextrins on the buccal permeation of a hydrophobic model drug, omeprazole was studied. First, the influence of the complexation with cyclodextrins in the absence and in the presence of an alkali agent, l-arginine, on the drug stability was checked at neutral conditions since omeprazole alone is only stable in basic conditions. In vitro transbuccal permeation of omeprazole non-complexed and complexed with β- and methyl-β-cyclodextrin and in presence of l-arginine was examined using freshly obtained porcine buccal mucosa. Tissue viability after incubation with sample solutions was assessed using a MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) biochemical assay and histological evaluation. The toxicity of the sample solutions on buccal mucosa was evaluated by measuring lactate dehydrogenase activity. The present results show that complexation with cyclodextrins increases drug stability at neutral conditions; furthermore, l-arginine contributed to higher drug stability. Permeation studies indicate an increase on drug permeation in complexed form of 1.1- and 1.7-fold for β-cyclodextrin and methyl-β-cyclodextrin, respectively. The presence of l-arginine increases drug permeation 1.4-fold in omeprazole complexed with β-cyclodextrin and 2.4-fold in the inclusion complex formed with methyl-β-cyclodextrin. The cell viability of the buccal mucosa after a 3 h incubation period, with all sample solutions, remained around 70% and lactate dehydrogenase assay showed that studied cyclodextrins, even in the presence of an alkali agent are not cytotoxic for porcine buccal mucosa. Histological evaluation of the tissue demonstrated that the buccal epithelium remains viable after 3 h of incubation with sample solutions.     

Novel buccal adhesive system for anti-hypertensive agent Nimodipine

Novel buccal adhesive system (NBAS) containing Nimodipine (N) was prepared and evaluated by different parameters such as weight uniformity, thickness, hardness, surface pH, swelling index, mucoadhesive strength (MS), in vitro drug release and ex vivo drug permeation. Different formulations containing 5–20% Carbopol 934 (CP) and SCMC HV in sustained release part and sodium alginate:chitosan lactate in different ratios (1:1, 2:1, 1:2, and 3:1) in fast release part were prepared and tested. NBAS containing CP 5% and SCMC HV and sodium alginate: chitosan lactate 1:1 was selected as a suitable formula based on the (MS) and the release profile. Compared to the conventional buccal adhesive tablet, NBAS showed an effective controlled release pattern with faster release at the initial period. The mechanism of N release was found to be by non-fickian diffusion, followed first order release kinetics. It can be considered that NBAS is a superior, novel system that overcomes the drawback associated with the conventional buccal adhesive tablet.     

Preparation & characterization of solid inclusion complex of cefpodoxime proxetil with beta-cyclodextrin

Cefpodoxime proxetil (CPDX-PR) is an oral cephalosporin antibiotic with poor aqueous solubility and bioavailability. Effect of beta-cyclodextrin on aqueous solubility and dissolution rate of cefpodoxime proxetil was evaluated by the formation of solid inclusion complexes in 1:2 molar ratio of drug: cyclodextrin. Phase solubility study was carried out whereby a typical B's type curve was obtained thus, indicating a 1:2 stoichiometric ratio for optimum complex formation. Solid inclusion complexes in 1:2 molar ratios were prepared by using methods such as physical mixture, solvent evaporation and freeze drying. Prepared complexes were characterized by fourier transform infrared spectroscopy (FT-IR) differential scanning calorimetry (DSC), powder x-ray diffraction (PXRD) and scanning electron microscopy (SEM). Results of in vitro studies appraised of an increased solubility and dissolution rate of cefpodoxime proxetil on complexation with beta- cyclodextrin (P < 0.05) as compared to CPDX-PR alone. Amongst the complexes prepared by different methods, the complex prepared by freeze drying showed the highest dissolution rate (P< 0.01). The in vitro antimicrobial activity of cefpodoxime proxetil and its freeze dried complex (1:2) was studied against both antibiotic-susceptible and antibiotic-resistant clinical isolates of Neisseria gonorrhoeae. The freeze dried complex (1:2) inhibited all penicillin-susceptible strains and penicillinase-producing strains at 0.015 microg/ml concentration. Chromosomally resistant strains which were not responsive to penicillin were inhibited by the complex at 0.125 microg/ml concentration. The study revealed that complexation of cefpodoxime proxetil with beta-cyclodextrin effectively enhanced the aqueous solubility and in vitro antibacterial activity.     

Hybrid drug delivery system for oropharyngeal,cervical and colorectal cancer – in vitro and in vivo evaluation

The present investigation was designed with the intention to formulate a versatile 5-fluorouracil(5-FU) matrix tablet surpassing issues associated with current conventional chemotherapeutic drug delivery systems. The novel 5-FU matrix tablet fulfills therapeutic needs by engineering matrix tablets utilizing chitosan–sodium alginate interpolyelectrolyte complex (IPEC). IPEC was characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The matrix tablets were formulated utilizing IPEC alone and in combination with chitosan, sodium alginate and sodium deoxycholate as permeation enhancer. Pharmaceutical properties, swelling studies, in vitro dissolution and diffusion studies, mucoadhesive studies and in vivo studies were performed for formulated 5-FU. The selected chitosan–sodium alginate IPEC offers pH independent 5-FU release in comparison to alone or physical mixture of chitosan and sodium alginate. Furthermore, novel matrix tablets demonstrated significantly higher bioadhesive properties with controlled 5-FU release without the initial burst effect and also demonstrated a higher permeation of 5-FU. To conclude, the developed novel 5-FU matrix tablets pave way as an excellent alternative for cancer treatment which could potentially minimize the dose dependent side effects and provide better patient compliance.