IN VIVO STUDY OF PROMISING FORMULATED OCULAR BIO-ADHESIVE INSERTS OF CIPROFLOXACIN HYDROCHLORIDE COMBINATION WITH XANTHAN GUM AND CARBOPOL

Objective: To study the in vivo behaviour and irritant properties of different ocular bio-adhesive inserts of ciprofloxacin hydrochloride (CFX-HCl) prepared using a spray dried (SD2) matrix system consisting of xanthan gum, carbopol, and propylene glycol.Methods: CFX-HCl in aqueous humor samples was analysed using HPLC method. Applying a mobile phase of 0.01M sodium acetate: methanol (70:30 v/v) with pH around 3.00, and using Purosphere star 100RP-18 column (125 mm × 4.6 mm × 5 µm). The in vivo behaviour and irritant properties of ocular inserts was studied on rabbits. Twelve rabbits were used for the study and were divided into four groups. After placing the insert in the eye 100 µl of the aqueous humor was withdrawn at different time intervals in order to measure the concentration profile of CFX-HCl. The tested formulae R, F1, F2, and F3 were all containing 6.25 mg of CFX-HCl.Results: The method was well validated according to linearity, recovery, and precision. Where the calibration curve was linear over a concentration range of (2.500–7.826) µg/ml, with an average recovery of 99.76%. The presence of the matrix system enhances the absorption of CFX-HCl and sustains its release up to four days leading to increasing its bioavailability. Also, the ocular inserts of F2 and F3 have better biocompatibility compared with R and F1.Conclusion: The analysis method was found sensitive, accurate and precise and could be used to assess the in vivobehaviour of CFX-HCl. The ratio of the free drug to the matrix system controlled the rate of drug release. Â

Razvoj i vrednovanje lako topljivih tableta kompleksa meloksikama s β-ciklodekstrinom pripravljenih izravnom kompresijom

The aim of this study was to prepare fast-dissolving tablets of meloxicam after its complexation with β-cyclodextrin (β-CD) and to investigate the effect of using different superdisintegrants on the disintegration and release of meloxicam from the tablets. A complex of meloxicam with β-CD was prepared by spray drying and then compressed in the form of tablets utilizing the direct compression technique. Three superdisintegrants were employed at various levels sodium starch glycolate, croscarmellose sodium, and crospovidone. Co-spray dried micro-crystalline cellulose and mannitol (Avicel HFE-102) were used as diluents in the tablets. Prior to compression, the pre-compression parameters showed satisfactory flow properties. Post-compression parameters showed that all tablet formulations had acceptable mechanical properties. Wetting and disintegration times were prolonged by increasing the level of sodium starch glycolate in the tablets. This was attributed to the formation of a viscous gel layer around the tablets by sodium starch glycolate whereas this effect was not observed with croscarmellose sodium and crospovidone. Dissolution studies showed fast release of meloxicam except in tablets containing a high level of sodium starch glycolate. Complexation of meloxicam with β-CD significantly improved the solubility of the drug and improved the mechanical properties of tablets produced by direct compression.Cilj rada bio je priprava lako topljivih tableta kompleksa meloksikama s β-ciklodekstrinom (β-CD) te ispitati utjecaj različitih superdezintegratora na raspadljivost tableta i oslobađanje meloksikama. Kompleks meloksikama s β-CD pripravljen je metodom sušenja sprejem, a komprimiran je u tablete metodom izravne kompresije. U pripravi tableta korištene su tri različite količine triju superdezintegratora: natrijev škrobni glikolat, natrijeva sol kroskarmeloze i krospovidon, dok su mikrokristalinična celuloza i manitol (Avicel HFE-102) upotrijebljeni kao punila. Predkompresijski parametri ukazivali su na zadovoljavajuću tečnost. Postkompresijski parametri pokazali su da sve tablete imaju prihvatljiva mehanička svojstva. Vlaženje i vrijeme raspadanja bilo je produljeno kada se povećao udio natrijevog škrobnog glikolata u tabletama. To je pripisano stvaranju viskoznog sloja gela oko tableta, što nije primijećeno u pripravi tableta s natrijevom soli kroskarmeloze i krospovidonom. Oslobađanje meloksikama bilo je brzo iz svih tableta, osim iz tableta s visokim udjelom natrijeve soli škrobnog glikolata. Kompleksiranje meloksikama s β-CD značajno je povećalo topljivost lijeka i poboljšalo mehanička svojstva tableta

Characterization of glucose-dependent gel-sol phase transition of the polymeric glucose-concanavalin A hydrogel system

Development of modulated insulin delivery devices is important for the control of diabetes because simple replacement of insulin by periodic injections is unable to prevent complications resulting from this disorder. Polymeric hydrogels have been studied extensively as potential devices to control the release of insulin. An ideal insulin delivery system would have the capability to sense the glucose level in the blood and release the appropriate amount of insulin. The main goal of this study was to synthesize and characterize hydrogels which undergo reversible gel-sol phase transformation in response to changes in glucose concentration in the surrounding environment. The glucose-sensitive hydrogels were made by mixing the appropriate concentrations of acrylamide-allyl glucose copolymer and concanavalin A (Con A). The efficacy of hydrogel formation increased as the copolymer concentration decreased at a fixed concentration of Con A. To examine their phase reversibility, hydrogels in dialysis membranes were cycled between glucose-free and glucose-containing buffers. The synthesized hydrogels underwent phase transition to sol in the presence of free glucose in the surrounding environment. The non-covalent crosslinking of glucose-containing polymer chains through Con A provides the gel-sol phase reversibility. The concentration of external free glucose had to be at least 4 times that of polymer-bound glucose to induce phase transition from gel to sol. Cooperative interactions between polymer-bound glucose and Con A were observed when the concentration of polymer-bound glucose in the gel was increased to 0.42 mg/ml. Above the concentration, external free glucose had to be much higher than 4 times that of polymer-bound glucose to induce phase transition to sol. The binding affinity study showed that binding of allyl glucose to Con A was 4 times stronger than that of free glucose to Con A. The non-linear dependence of phase transition was explained by the increased binding affinity of allyl glucose over native glucose to Con A, and the cooperative interactions between polymer-bound glucose and Con A. The hydrogel membranes were found to control the release of proteins, such as insulin and lysozyme, in response to the changing concentration of free glucose

Preparation of Mucoadhesive Oral Patches Containing Tetracycline Hydrochloride and Carvacrol for Treatment of Local Mouth Bacterial Infections and Candidiasis

The specific aim of this work was to prepare mucoadhesive patches containing tetracycline hydrochloride and carvacrol in an attempt to develop a novel oral drug delivery system for the treatment of mouth infections. The bilayered patches were prepared using ethyl cellulose as a backing layer and carbopol 934 as a matrix mucoadhesive layer. Patches were prepared with different loading amounts of tetracycline hydrochloride and carvacrol. The antimicrobial activity was assessed for the prepared patches using the disc-diffusion method against the yeast Candida albicans and five bacterial strains, including Pseudomonas aeruginosa, Escherichia coli, Bacillus cereus, Staphylococcus aureus, and Bacillus bronchispti. In this work, we highlighted the possibility of occurrence of a synergistic action between carvacrol and tetracycline. The best formulation was selected based on microbiological tests, drug release, ex-vivo mucoadhesive performance, and swelling index. Physical characteristics of the selected formulations were determined. These included pH, patch thickness, weight uniformity, content uniformity, folding endurance, and patch stability

Sustained-release diclofenac potassium orally disintegrating tablet incorporating eudragit ERL/ERS:Possibility of specific diclofenac-polymer interaction

Sustained-release diclofenac potassium orally disintegrating tablet (ODT) formulations have been prepared and investigated. The ODTs were prepared by incorporating diclofenac potassium (DP), as a model for negatively ionizable drugs, in microcapsules that were prepared by the solvent evaporation method from a mixture of DP and different ratios of Eudragit RS and Eudragit RL, which are positively ionized synthetic polymers. The ODTs were prepared by direct compression of mixtures containing microcapsule formula M4, crospovidone as a superdisintegrant and water soluble excipients (mannitol or lactose and sorbitol). Diclofenac potassium ODT F2, showed acceptable hardness (4.08 KP) slight friability (2.13 %) and disintegration time of 22.41 s with a sustained drug release profile. Microcapsule characterization (DSC and FT-IR) and dissolution behavior suggests the presence of specific interaction between the carboxylate group of diclofenac and the quaternary ammonium group in the polymers</p

Assessment of patient-controlled analgesia versus intermittent opioid therapy to manage sickle-cell disease vaso-occlusive crisis in adult patients

Background: Vaso-occlusive crisis (VOC) is one of the acute complications of sickle-cell disease (SCD). Treatment mainly relies on hydration and pain control by analgesics. The specific aim of this study was to assess potential health outcomes within the first 72 h of admission between intermittent and patient-controlled analgesia (PCA) by opioids among VOC patients. Methods: A retrospective chart review study was conducted to determine SCD patients with VOC. Using the hospital electronic system, the following data were collected: patient's age, gender, blood pressure, heart rate, respiratory rate, oxygen saturation, and pain score on admission and daily for 3 days as well as the cumulative opioid analgesic dose for 72 h which is reported as morphine equivalent. Results: One hundred and seventeen patients were screened over a period of 5 years. Of those, 99 (84.6%) met the study inclusion criteria, and 18 patients (15.4%) were excluded from the study. During the first 72 h of admission, a significant reduction in pain score was observed in patients on intermittent intravenous (IV) administration compared to those in the PCA group (P < 0.0004) where the mean pain scores were 3 and 5, respectively. The total amount of morphine administered over 72 h of admission was significantly higher in PCA group (777 ± 175 mg) as compared to the intermittent IV administration group (149 ± 74 mg) (P < 0.000003). Clinically significant hypotension or respiratory depression was not observed in both groups over the 72 h of admission. Conclusion: During the first 72 h of admission, intermittent IV administration of morphine was more effective than PCA infusion in pain control

Optimized Polyethylene Glycolylated Polymer–Lipid Hybrid Nanoparticles as a Potential Breast Cancer Treatment

Purpose: The aim of this work is to optimize a polyethylene glycolated (PEGylated) polymer&ndash;lipid hybrid nanoparticulate system for the delivery of anastrozole (ANS) to enhance its biopharmaceutical attributes and overall efficacy. Methods: ANS loaded PEGylated polymer&ndash;lipid hybrid nanoparticles (PLNPs) were prepared by a direct emulsification solvent evaporation method. The physical incorporation of PEG was optimized using variable ratios. The produced particles were evaluated to discern their particle size and shape, zeta-potential, entrapment efficiency, and physical stability. The drug-release profiles were studied, and the kinetic model was analyzed. The anticancer activity of the ANS PLNPs on estrogen-positive breast cancer cell lines was determined using flow cytometry. Results: The prepared ANS-PLNPs showed particle sizes in the range of 193.6 &plusmn; 2.9 to 218.2 &plusmn; 1.9 nm, with good particle size uniformity (i.e., poly-dispersity index of around 0.1). Furthermore, they exhibited relatively low zeta-potential values ranging from &minus;0.50 &plusmn; 0.52 to 6.01 &plusmn; 4.74. The transmission electron microscopy images showed spherical shape of ANS-PLNPs and the compliance with the sizes were revealed by light scattering. The differential scanning calorimetry DSC patterns of the ANS PLNPs revealed a disappearance of the characteristic sharp melting peak of pure ANS, supporting the incorporation of the drug into the polymeric matrices of the nanoparticles. Flow cytometry showed the apoptosis of MCF-7 cell lines in the presence of ANS-PLNPs. Conclusion: PEGylated polymeric nanoparticles presented a stable encapsulated system with which to incorporate an anticancer drug (ANS) with a high percentage of entrapment efficiency (around 80%), good size uniformity, and induction of apoptosis in MCF-7 cells