Development and optimization of solid lipid nanoparticles coated with chitosan and poly(2-ethyl-2-oxazoline) for ocular drug delivery of ciprofloxacin

Many formulation strategies have been employed to improve ocular bioavailability of topical eye drops. The aim of this study was to develop and evaluate a series of solid lipid nanoparticles coated with poly(2-ethyl-2-oxazoline) and chitosan for ocular delivery of ciprofloxacin. Ciprofloxacin-loaded poly(2-ethyl-2-oxazoline) (PSLN) formulation was prepared by a combination of melt-emulsion sonication and low-temperature solidification methods. A Box-Behnken design, was employed to statistically optimize the effects of the amount of drug (X1), lipid:polymer ratio (X2) and surfactant concentration (X3) on particle size (Y1) and entrapment efficiency (Y2). Analysis of variance was used to validate the optimization design; and regression equations and response surface plots were generated. The optimized formulation was selected through numerical point prediction approach. These nanoparticles were characterized using dynamic light scattering, transmission electron microscopy (TEM), differential scanning calorimetry (DSC), and powder X-ray diffractometry (PXRD). In vitro drug release and corneal permeation studies were carried out, while the mucoadhesive properties were evaluated ex vivo using porcine corneal tissue. The particle size and zeta potential of the optimized formulations ranged from 141.3 to 213.0 nm and +24.6 to −35.6 mV, respectively. PSLN possessed higher encapsulation efficiency than chitosan-coated solid lipid nanoparticles (CSLN). The in vitro drug release from all the formulations showed an initial burst release followed by prolonged release over 24 h. The release mechanism followed Korsemeyer-Peppas model and Fickian diffusion (n < 0.5). DSC revealed lower enthalpy and crystallinity of the formulations as also detected by PXRD, while TEM showed spherical particles in the lower nanometer range with a layer of polymer coating. The results of this study demonstrated that CSLN exhibited higher mucoadhesion and retention on corneal tissues compared with PSLN and also showed higher flux and apparent permeability, but with lower entrapment efficiency

Formulation and characterization of artemether-loaded sodium alginate microcapsules

Purpose: To increase the solubility of artemether (ART) in Transcutol® HP through microencapsulation in sodium alginate polymer to achieve&nbsp; sustained in vivo release.Method: Graded concentrations of ART (0.00, 0.25, 0.50, 0.75, and 1.00 g) microcapsules were produced using Tween® 80 by the cold&nbsp; homogenization method at 24 x 1000 rpm for 15 min. Characterization based on yield, encapsulation efficiency (EE), particle size, pH stability,&nbsp; differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and in vivo release using Peter’s four-day suppressive protocol in Wistar mice infected with Plasmodium berghei, were determined.Results: The results obtained indicate that 0.5 g ART-loaded microcapsules (AMC) showed the highest yield of 96.85 %. The EE of 88.3 %&nbsp; corresponded to 0.75 g ART-loaded microcapsules. DSC results revealed that there was a significant reduction in enthalpy in all the formulations compared to the crystalline drug, but no strong bond interaction occurred except for the blank microcapsules. The AMC1.0 showed high dose-dependent plasmodial growth inhibition of 88.75 % while AMC0.25 had the least (68.13 %).Conclusion: The artemether microcapsules showed sustained release characteristics for oral delivery of artemether and therefore may reduce some of the adverse effects associated with high dose artemether therapy in conventional oral tablets. Keywords: Malaria, Artemether, Transcutol® HP, Sustained-release, RBC count, Antiplasmodial activit

Effect of pH and ionic strength on the bioadhesive properties of Prosopis africana gum

Prosopis gum (PG) extracted from Prosopis africana was investigated for bioadhesive properties as affected by pH and ionic strength. The bioadhesive properties were evaluated using the adhesion of gum dispersion-coated glass beads on the antrum region of the porcine gastrointestinal tract and Lecomte Du Nouy tensiometer. Results obtained indicated that prosopis gum is highly bioadhesive and that increase in both ionic strength and pH favour bioadhesion. By implication, PG can be used to target drugs intended to release in the small intestine and that way drugs sensitive to acidic pH, enzymatic attacks in the stomach or those that cause unbearable gastric irritation may be good candidates for bioadhesive drug delivery using Prosopis africana as the bioadhesive material. Keywords: bioadhesion, ionic strength, pH, Prosopis africana gum Journal of Pharmacy & Bioresources Vol. 2(2) 2005: 141-14

Development of artemether-loaded nanostructured lipid carrier (NLC) formulation for topical application.

NLC topical formulation as an alternative to oral and parenteral (IM) delivery of artemether (ART), a poorly water-soluble drug was designed. A Phospholipon 85G-modified Gelucire 43/01 based NLC formulation containing 75% Transcutol was chosen from DSC studies and loaded with gradient concentration of ART (100-750mg). ART-loaded NLCs were stable (-22 to -40mV), polydispersed (0.4-0.7) with d90 size distribution range of 247-530nm without microparticles up to one month of storage. The encapsulation efficiency (EE%) for ART in the NLC was concentration independent as 250mg of ART loading achieved ∼61%. DSC confirmed molecular dispersion of ART due to low matrix crystallinity (0.028J/g). Ex vivo study showed detectable ART amounts after 20h which gradually increased over 48h achieving ∼26% cumulative amount permeated irrespective of the applied dose. This proves that ART permeates excised human epidermis, where the current formulation served as a reservoir to gradually control drug release over an extended period of time. Full thickness skin study therefore may confirm if this is a positive signal to hope for a topical delivery system of ART

Novel anti-ulcer phytosomal formulation of ethanol extract of pentaclethra macrophylla stem-bark

Pentaclethra macrophylla, a medicinal plant widely used for ulcer treatment in Nigeria by herbal practitioners, is limited by poor lipid solubility, resulting in poor absorption and bioavailability. Phytosomes, a novel dosage form that are better absorbed and produce better results than conventional herbal extracts, could be employed to enhance its antiulcer activity. The objective of this study was to formulate Pentaclethra macrophylla stem-bark extract as phytosomes by forming complexes with phospholipid and compare the antiulcer activity with omeprazole, a standard anti-ulcer drug. Phytosomal formulations of ethanol extract of Pentaclethra macrophylla stem-bark and Phospholipon® 90G (P90G) (extract:P90G ratios of 1:1, 1:3, 1:5) were prepared following established method. Their physicochemical properties, in vitro drug release in simulated intestinal fluid (SIF, pH=7.4) and simulated gastric fluid (SGF, pH=1.2) and anti-ulcer properties on aspirin-induced ulcer using Wistar rats were determined and compared with omeprazole. Phytosomes with spherical smooth particles with size range 0.106-0.217 µm and good encapsulation efficiencies (range = 67.61-72.8%) were obtained. Drug release increased with time irrespective of phospholipid concentration or dissolution medium. The extract possessed antiulcer activity (23.33%) which was increased to 33.33, 43.33 and 56.67% by formulating it as phytosomal formulations containing extract:P90G ratios of 1:1, 1:3, 1:5, respectively. However, omeprazole and its formulations gave significantly (p<0.05) greater antiulcer activity when compared with both the ethanol extract and phytosomes. Pentaclethra macrophylla stem-bark possessed antiulcer activity, which was improved via phytosomal formulation. This would serve as potential safer and cheaper alternative therapeutics for ulcer given the side-effects associated with omeprazole

Studies on the Charge-TransferInteraction Between TamoxifenCitrate and Chloranilic Acid: Charge-transfer between tamoxifen and chloranilic acid

The complex formed as a consequence of the interaction between the electron-acceptor P-chloranilic acid and an electron donor tamoxifen citrate was employedin the assay of the drug in pure powder and tablets. Chloranilic acid was found toform a charge-transfer complex in a 1:1 stoichiometric ratio, with tamoxifen citrate.The wavelength of maximum absorption for the complex was found to be 550 nmwhile the absorbance was linear over the concentration range of 2-100 g/ml.Evaluations of the various thermodynamic parameters by means of the Scottequation was carried out and were found to decrease with increase in temperature.The free energy change (ΔG°) and the enthalpy of formation (ΔH°) as well as theentropy (ΔS°) were determined for various interactions. Results obtained suggestthat the proposed method may be conveniently applied in the analysis ofcommercially available tamoxifen citrate tablets with a high degree of accuracy andreproducibility

Formulation and evaluation of transdermal nanogel for delivery of artemether.

rtemether (ART) is second to artesunate in being the most widely used derivatives of artemisinin in combination therapy of malaria. Nanostructured lipid carrier (NLC) formulations were prepared following our previous report using optimized ART concentration of 0.25 g dissolved in 5% w/v mixture of solid (Gelucire 43/01 and Phospholipon 85G) and liquid (Transcutol) lipids at 90 °C. An aqueous surfactant phase at 90 °C was added (dropwise) under magnetic stirring (1000 rpm) for 5 min. The pre-emulsion was speedily homogenized at 28,000 rpm for 15 min and further probe sonicated at 60% amplitude (15 min). Resultant sample was cooled at room temperature and frozen at - 80 °C prior to lyophilization. The freeze-dried sample was used for solid-state characterization as well as in the formulation of transdermal nanogels using three polymers (Carbopol 971P, Poloxamer 407, and Prosopis africana peel powder) to embed the ART-NLC, using ethanol as a penetration enhancer. Transdermal ART-nanogels were characterized accordingly (physical examination, pH, drug content, rheology, spreadability, stability, particle size and morphology, skin irritation, in vitro and ex vivo skin permeation, and analysis of permeation data), P C971P-ANG. A two-patch/week concurrent application of the studied nanogels could offer 100% cure of malaria as a lower-dose (50 mg ART) patient-friendly regimen devoid of the drug's many side effects