Controlled release behaviour of protein-loaded microparticles prepared via coaxial or emulsion electrospray

Biodegradable poly (lactic-co-glycolic acid) (PLGA) microparticles are an effective way to achieve sustained drug release. In this study, we investigated a sustained release model of PLGA microparticles with incorporated protein via either emulsion or coaxial electrospray techniques. PLGA (75:25) was used as the carrier, and bovine serum albumin as a model protein. Coaxial electrospray resulted in a type of core–shell structure with mean diameters of 2.41?±?0.60?µm and a centralised protein distribution within the core. Emulsion electrospray formed bigger microparticles with mean diameters of 22.75?±?8.05?µm and a heterogeneous protein distribution throughout the microparticles. The coaxial electrospray microparticles presented a much slighter burst release than the emulsion electrospray microparticles. Loading efficiency was significantly higher (p?<?0.05) in the coaxial group than emulsion group. This indicated that both emulsion and coaxial electrospray could produce protein-loaded microparticles with sustained release behaviour, but the former revealed a superior approach for drug delivery.     

The effect of homogenization method on the properties of carbamazepine microparticles prepared by spray congealing

Abstract

The aim of this study was to investigate the influence of ultrasound and high-shear mixing on the properties of microparticles obtained by spray congealing. Dispersions containing 10% carbamazepine and 90% carrier Gelucire® 50/13 (w/w) were prepared using magnetic stirring, high-shear mixing, or ultrasound. Each preparation was made using hot-melt mixing spray congealing to obtain the microparticles. All microparticles presented a spherical shape with high encapsulation efficiency (>99%). High-shear mixing and ultrasound promoted a decrease in the size of microparticles (D₉₀) to 62.8?±?4.1?μm and 64.9?±?3.3?μm, respectively, while magnetic stirring produced microparticles with a size of 84.1?±?1.4?µm. The use of ultrasound led to microparticles with increased moisture content as identified through sorption isotherm studies. In addition, rheograms showed distinct rheological behaviour among different dispersion preparations. Therefore, the technique used to prepare dispersions for spray congealing can affect specific characteristics of the microparticles and should be controlled during the preparation.     

Encapsulation of a pressure-sensitive adhesive by spray-drying: microparticles preparation and evaluation of their crushing strength

An industrial pressure-sensitive adhesive was microencapsulated by spray-drying using an aqueous colloidal ethylcellulose dispersion (Aquacoat? ECD) plasticised by triacetin to form the wall material. Unloaded (0:100) and adhesive-loaded (25:75) particles were produced in a Büchi B-191 mini spray-dryer with product yields of 62% and 57%, respectively. Microparticles were spherical and narrow sized with mean D?,? diameters of 3.165?±?0.001 and 5.544?±?0.105?μm, respectively. The microparticles were found to redisperse well in water and exhibit enough stability in neutral and alkaline aqueous media to be further used in a coating slip. Crush tests on single microparticles with diameters ranging from 2 to 12 μm were performed using a nanoindenter. They revealed that the crushing force of both kinds of microparticles increased linearly with their diameter and that the adhesive loading reduced the mechanical strength of the prepared microparticles.     

The ocular surface side effects of an anti-psychotic drug,clozapine

Purpose: The purpose of this study is to investigate the effects of long-term clozapine usage on tear film stability and corneal topographic parameters.

Material and methods: The study was conducted between March 2014 and November 2014. Thirty patients who were diagnosed of schizophrenia and have been under clozapine treatment for 2.73?±?0.73 years (range 2–4 years) were involved in this study (group 1). Thirty healthy subjects (group 2) who have statistically similar demographic features compared with the group 1, were involved as a control group. Full ophthalmologic examination with biomicroscopy and indirect ophthalmoscopy was applied. Corneal topographic parameters were measured using the Pentacam HR and Schirmer test was done. Statistical analysis of the subjects was evaluated by using SPSS (for Windows version 16.0; SPSS Inc., Chicago, IL) program.

Results: K₁ value was measured as 43.39?±?0.17?D (43–43.50?D) and K₂ value was measured as 43.39?±?0.06?D (43.30–43.50?D) in groups 1 and 2, respectively. In groups 1 and 2, K₂ values were noted as 43.86?±?0.27?D (43.50–44.50?D) and 43.72?±?0.18?D (43.50–44.00?D), respectively. Central corneal thickness was found to be 523.93?±?15.66?µm (495–554?µm) and 550.13?±?1.03?µm (520–580?µm) in groups 1 and 2, respectively. Corneal apex thickness was 525.86?±?15.75?µm (497–556?µm) in group 1 and 551.60?±?14.99?µm (521–581?µm) in group 2. The corneal thickness of thinnest location was 520.93?±?15.60?µm (492–551?µm) and 548.06?±?15.17?µm (518–578?µm) in groups 1 and 2, respectively. Corneal volume was determined as 58.13?±?3.46?mm³ (52–64?mm³) in group 1 and 60.73?±?3.76?mm³ (54–66?mm³) in group 2. The Schirmer test showed thichkness of 3.33?±?0.72?mm (2–4?mm) and 13.60?±?1.59?mm (11–16?mm) in groups 1 and 2, respectively. The mean fluorescein break-up time was 5.40?±?1.50?s (3–8?s) and 12.46?±?1.40?s (10–14?s) in groups 1 and 2, respectively. There was a statistically significant difference in the Schirmer test, fluorescein break-up time, central corneal thickness, corneal apex, and the thinnest corneal location thickness between the two groups.

Conclusion: Clozapine may induce dry eye syndrome and thus may lead to morphological alterations in corneal parameters through its anticholinergic and antidopaminergic activities. Because of these corneal alterations, one should be aware of evaluating patients having diseases like glaucoma or preoperative selection of corneal refractive surgery candidates.     

Inactive Vibrio cholerae whole-cell vaccine-loaded biodegradable microparticles: in vitro release and oral vaccination

An approach is proposed using Vibrio cholerae (VC)-loaded microparticles as oral vaccine delivery systems for improved vaccine bioavailability and increased therapeutic efficacy. The VC-loaded microparticles were prepared with 50:50 poly(DL-lactide-co-glycolide) (PLG), 75:25 poly(DL-lactide-co-glycolide) and poly(lactide acid) (PLA)/PEG blend copolymers by the solvent evaporation method. VC was successfully entrapped in three types of microparticles with loading efficiencies and loading levels as follows: 50:50 PLG systems: 97.8% and 55.4 ± 6.9 µg/mg; 75:25 PLG systems: 89.2% and 46.5 ± 4.4?µg/mg; PLA/PEG-blended systems: 82.6% and 53.7 ± 5.8?µg/mg. The different distributions of VC in the core region and on the surface were as follows: 50:50 PLG systems 25.7 ± 1.9 and 6.2 ± 0.9?µg/mg; 75:25 PLG systems: 25.8 ± 2.2 and 3.6 ± 0.4?µg/mg; PLA/PEG-blended systems: 32.4 ± 2.1 and 5.2 ± 1.0?µg/mg, respectively. In vitro active release of VC was affected mainly by matrix type and VC-loaded location in microparticles. The therapeutic immunogenic potential of VC loaded with 50:50 PLG, 75:25 PLG and PLA/PEG-blended microparticles was evaluated in adult mice by oral immunization. Significantly higher antibody responses and serum immunoglobin Ig G, IgA and IgM responses were obtained when sera from both VC-loaded 75:25 PLG and PLA/PEG-blended microparticles immunized mice were titrated against VC. The most immunogenicity in evoking serum IgG, IgA and IgM responses was immunized by VC-loaded PLA/PEG-blended microparticles, and with VC challenge in mice, the survival rate (91.7%).     

Investigating the effects of surfactants on the size and hydrolytic stability of poly(adipic anhydride) particles

The present study investigates the effects of surfactants (<0.01% v/v) on the size and hydrolytic stability of poly(adipic anhydride) (pAA) micro- and nanospheres fabricated using a modified phase inversion technique. Overall, surfactants increased the output yield by roughly 20%. Lecithin produced the greatest reduction in the volumetric particle size (d_vol) compared to particles fabricated with no surfactant (d_vol?=?530?±?300?nm and 2.2?±?1.1?µm, respectively). In addition, sorbitan monooleate produced spheres with smaller numeric diameters (d_num) than the control but appeared to induce aggregation (d_vol?=?7.7?±?12.5?µm). The d_num and d_vol were not dependent on the hydrophobicity of the surfactant (R²?=?0.36 and 0.03, respectively) or the apparent surface tension of the non-solvent (NS) phase (R²?=?0.44 and 0.04, respectively). In addition, quantitative DSC and FT-IR analysis confirmed that altering the particle size could also influence the hydrolytic stability of pAA.     

Colon-targeted celecoxib-loaded Eudragit® S100-coated poly-ϵ-caprolactone microparticles: Preparation,characterization and in vivo evaluation in rats

Context: Celecoxib suffers from low and variable bioavailability following oral administration of solutions or capsules. Recent studies proved that chemoprevention of colorectal cancer is possible with celecoxib.

Objective: This work aimed to tailor colon-targeted celecoxib-loaded microparticles using time-dependant and pH-dependant coats. Estimation of drug pharmacokinetics following oral administration to fasted rats was another goal.

Methods: A 2³ factorial design was adopted to develop poly-?-caprolactone (PCL) celecoxib-loaded microparticles (F1–F8). To minimize drug-percentages released before colon, another coat of Eudragit^® S100 was applied. In vitro characterization of microparticles involved topography, determination of particle size and entrapment efficiency (EE %). Time for 50% drug release (t_50%) and drug-percentages released after 2 hours (Q_2h) and 4 hours (Q_4h) were statistically compared. Estimation of drug pharmacokinetics following oral administration of double-coat microparticles (F10) was studied in rats.

Results: PCL-single-coat microparticles were spherical, discrete with a size range of 60.66?±?4.21–277.20?±?6.10 μm. Direct correlations were observed between surfactant concentration and EE%, Q_2h and Q_4h. The PCL M.wt. and drug: PCL ratio had positive influences on EE% and negative impacts on Q_2h and Q_4h. When compared to the best achieved PCL-single-coat microparticles (F2), the double-coat microparticles (F10) showed satisfactory drug protection; Q_2h and Q_4h were significantly (P?<?0.01) decreased from 31.84?±?1.98% and 54.72?±?2.10% to 15.92?±?1.78% and 26.93?±?2.76%, respectively. When compared to celecoxib powder, F10 microparticles enhanced the bioavailability and extended the duration of drug-plasma concentration in rats.

Conclusion: The developed double-coat microparticles could be considered as a promising celecoxib extended-release colon-targeting system.     

Preparation and characterization of textile-based carrier systems for anal fissure treatment

Anal fissure is common and painful disease of anorectum. In this study, microparticles containing nifedipine and lidocaine HCl were prepared by spray drying and applied to bio-degradable and bio-stable tampons. Characterization of microparticles was determined by visual analyses, mass yield, particle size measurement, encapsulation efficiency, drug loading and in vitro drug release. Mass yield was between 5.5 and 45.9%. The particle size was between 15.1 and 26.8?µm. Encapsulation efficiency were 96.142?±?5.931 and 85.571?±?3.301; drug loading were 65.261?±?3.914% and 37.844?±?4.339% of L2 and N1, respectively. Well-separated, mainly spherical microparticles with suitable properties were obtained. Optimum microparticles were applied to tampons. Physical properties and visual characteristics of tampons were investigated before and after binder application. In vitro drug release from tampons were also examined. According to the results, textile-based carrier systems loaded microparticles containing nifedipine and lidocaine HCl will be an effective and promising alternative for current anal fissure treatment.     

Identification of cytochrome P450 enzymes involved in the metabolism of 3′,4′-methylenedioxy-α-pyrrolidinopropiophenone (MDPPP), a designer drug,in human liver microsomes

The metabolism of 3′,4′-methylenedioxy-α-pyrrolidinopropiophenone (MDPPP), a novel designer drug, to its demethylenated major metabolite 3′,4′-dihydroxy-pyrrolidinopropiophenone (di-HO-PPP) was studied in pooled human liver microsomes (HLM) and in cDNA-expressed human hepatic cytochrome P450 (CYP) enzymes. CYP2C19 catalysed the demethylenation with apparent K_m and V_max values of 120.0?±?13.4?µM and 3.2?±?0.1?pmol/min/pmol?CYP, respectively (mean?±?standard deviation). CYP2D6 catalysed the demethylenation with apparent K_m and V_max values of 13.5?±?1.5?µM and 1.3?±?0.1 pmol/min/pmol?CYP, respectively. HLM exhibited a clear biphasic profile with an apparent K_m,1 value of 7.6?±?9.0 and a V_max,1 value of 11.1?±?3.6?pmol/min/mg?protein, respectively. Percentages of intrinsic clearances of MDPPP by specific CYPs were calculated using the relative activity factor (RAF) approach with (S)-mephenytoin-4′-hydroxylation or bufuralol-1′-hydroxylation as index reactions for CYP2C19 or CYP2D6, respectively. MDPPP, di-HO-PPP and the standard 4′-methyl-pyrrolidinohexanophenone (MPHP) were separated and analysed by liquid chromatography-mass spectrometry in the selected-ion monitoring (SIM) mode. The CYP2D6-specific chemical inhibitor quinidine (3?µM) significantly (p?相似文献   

Spray-dried microparticles: a potential vehicle for oral delivery of vaccines

This study aims to formulate a microparticle-based system that protects the protein from the harsh gastric conditions and also provides appropriate uptake via M cells for desired immune response upon oral administration. The formulation was derived using a valid statistical model, analysed by JMP® (SAS). The average size and charge of the resulting microparticles were 1.51?±?0.125?µm and?+?15.7?±?2.5?mV, respectively. Moreover, the particles provided a prolonged release over a period of 8?hrs which ensures M-cell uptake of intact particle with antigen (Kunisawa et al., 2011). This was further supported with in vivo studies where particle uptake was found in Peyer's patches of small intestine when observed for 8?h. Thus, these microparticles can be used as an efficient vaccine delivery vehicle upon oral administration.     

Chitosan-based macrophage-mediated drug targeting for the treatment of experimental visceral leishmaniasis

The potential of chitosan microparticles as a carrier of doxorubicin for the treatment of visceral leishmaniasis was evaluated by macrophage-mediated drug targeting approach. Cationic charge of doxorubicin was masked by complexing it with dextran sulphate (a poly anion) in order to facilitate its incorporation into cationic chitosan microparticles. Prior to in vitro and in vivo studies, characterization studies were carried out systematically: particle size (～1.049?µm), surface morphology (fluorescence microscopy – spherical structured microparticles), Fourier transform infrared spectroscopy (to characterize effective cross-linking) and differential scanning calorimetry. In vitro studies were carried out in J774.1 in order to check the effective endocytotic uptake of microparticles by macrophages. In vivo studies were conducted in Syrian golden hamsters as per well-established protocols and the results drawn from in vivo studies displayed substantial reduction in leishmanial parasite load for doxorubicin-encapsulated chitosan microparticles: ～78.2?±?10.4%, when compared to the control (free doxorubicin): 33.3?±?2.4%.     

In vitro antioxidant and anti-cholinesterase activities of Rhizophora mucronata

Context: Rhizophora mucronata Lam. (Rhizophoraceae), commonly known as Asiatic mangrove, has been used traditionally among Asian countries as folk medicine.

Objective: This study investigates the cholinesterase inhibitory potential and antioxidant activities of R. mucronata.

Materials and method: Rhizophora mucronata leaves were successively extracted using solvents of varying polarity and a dosage of 100–500?µg/ml were used for each assay. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities were assessed according to the method of Ellman. In vitro antioxidant activity was assessed using free radical scavenging, reducing power, and metal-chelating activity (duration – 3 months). Total phenolic and flavonoid content were quantified spectrophotometrically. Compound characterization was done using column chromatography, NMR, FTIR, and LC-MS analysis.

Results: Methanolic leaf extract (500?µg/ml) exhibited the highest inhibitory activity against AChE (92.73?±?0.54%) and BuChE (98.98?±?0.17%), with an IC₅₀ value of 59.31?±?0.35 and 51.72?±?0.33?µg/ml, respectively. Among the different solvent extracts, methanolic extract exhibited the highest antioxidant activity with an IC₅₀ value of 47.39?±?0.43, 401.45?±?18.52, 80.23?±?0.70, and 316.47?±?3.56?µg/ml for DPPH, hydroxyl, nitric oxide radical, and hydrogen peroxide, respectively. Total polyphenolic and flavonoid contents in methanolic extract were observed to be 598.13?±?1.85?µg of gallic acid equivalent and 48.85?±?0.70?μg of rutin equivalent/mg of extract. Compound characterization illustrated (+)-catechin as the bioactive compound responsible for cholinesterase inhibitory and antioxidant activities.

Conclusion: The presence of rich source of flavonoids, in particular catechin, might be responsible for its cholinesterase inhibitory and antioxidant activities.     

5-Fluorouracil-loaded microspheres prepared by spray-drying poly(D,L-lactide) and poly(lactide-co-glycolide) polymers: Characterization and drug release

5-Fluorouracil (5-FU), a hydrosoluble anti-neoplastic drug, was encapsulated in microspheres of poly(D,L-lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) polymers using the spray-drying technique, in order to obtain small size microspheres with a significant drug entrapment efficiency. Drug-loaded microspheres included between 47?±?11 and 67?±?12?µg 5-FU?mg^?1 microspheres and the percentage of entrapment efficiency was between 52?±?12 and 74?±?13. Microspheres were of small size (average diameter: 0.9?±?0.4–1.4?±?0.8?µm microspheres without drug; 1.1?±?0.5–1.7?±?0.9?µm 5-FU-loaded microspheres) and their surface was smooth and slightly porous, some hollows or deformations were observed in microspheres prepared from polymers with larger T_g. A fractionation process of the raw polymer during the formation of microspheres was observed as an increase of the average molecular weight and also of T_g of the polymer of the microspheres. The presence of 5-FU did not modify the T_g values of the microspheres. Significant interactions between the drug and each one of the polymers did not take place and total release of the included drug was observed in all cases. The time needed for the total drug release (28–129?h) was in the order PLA?>?PLGA 75/25?>?PLGA 50/50. A burst effect (17–20%) was observed during the first hour and then a period of constant release rate (3.52?±?0.82–1.46?±?0.26?µg 5-FU?h^?1 per milligram of microspheres) up to 8 or 13?h, depending on the polymer, was obtained.     

In vivo and in vitro characteristics for insulin-loaded PLA microparticles prepared by w/o/w solvent evaporation method with electrolytes in the continuous phase

Insulin-loaded poly(lactide) (PLA) microparticles were successfully prepared by 6% w/v PLA in the organic phase, 10% w/v PVP and varied types of 5%w/v electrolytes in the continuous phase, by using a water-in-oil-in-water emulsion/solvent extraction technique. Addition of electrolytes such as NaCl, CaCl₂ into the external phase significantly improved insulin entrapment efficiency compared to the case of no additives. NaCl was the most effective for obtaining high entrapment efficiency, with microparticle yield 81.2%, trapping efficiencies 49%, insulin-loading level 5.5% w/w and mean particle size 14.8?µm. The distribution (%) of insulin on the PLA microparticles surface, outer layer and core were 8, 37 and 43%, respectively. The cumulative release of insulin had an upper limit of ～24% of the insulin load at 24 days. A steady release rate was 0.5?µg insulin/mg microparticles/day of insulin release maintained for 24 days. Total protein-leaking amount was reduced after addition of electrolytes in the continuous aqueous phase. Rabbit glucose levels were evaluated after subcutaneous 20?mg insulin-loaded PLA microparticles or PLA blank microparticles. Study results show that the insulin-loaded PLA microparticles significantly reduced the glucose level than PLA blank microparticles. The insulin-loaded PLA microparticles, physicochemical characterization data and the animal result obtained in this study may be relevant in optimizing the PLA microparticle formulation incorporation and delivery insulin carriers.     

Embelin-loaded guar gum microparticles for the management of ulcerative colitis

The aim of the present study is to develop embelin-loaded guar gum microparticles through emulsification technique. The in vitro release of the optimised formulation was found to be 88.5?±?3.8% in 24?h, has exhibited remarkably sustain and delayed the release of embelin at a specific site. Embelin-loaded microparticles showed average particle size of 12.9?±?0.75?µm. The statistical analysis was carried out by one-way ANOVA followed by comparison test of Bonferroni. P values in vivo study concluded that pre-treatment of embelin prevents dinitrobenzenesulfonic acid (DNBS)-induced colitis in rats and depicts protective activity against ulcerative colitis due to its antioxidant and anti-inflammatory actions. This approach produces comparatively less side effect to another conventional dosage form.     

Preparation of novel solid lipid microparticles loaded with gentamicin and its evaluation in vitro and in vivo

Objective: To formulate and evaluate solid-reversed-micellar-solution (SRMS)-based solid lipid microparticles (SLMs) for intramuscular administration of gentamicin.

Methods: SRMS formulated with Phospholipon® 90G and Softisan® 154 were used to prepare gentamicin-loaded SLMs. Characterizations based on size and morphology, stability and encapsulation efficiency (EE%) were carried out on the SLMs. In vitro release of gentamicin from the SLMs was performed in phosphate buffer while in vivo release studies were conducted in rats.

Results: Maximum EE% of 90.0, 91.6 and 83.0% were obtained for SLMs formed with SRMS 1:1, 1:2 and 2:1, respectively. Stable, spherical and smooth SLMs of size range 9.80?±?1.46?µm to 33.30?±?6.42?µm were produced. The release of gentamicin in phosphate buffer varied widely with the lipid contents. Moreover, significant (p?<?0.05) amount of gentamicin was released in vivo from the SLMs.

Conclusion: SRMS-based SLMs would likely offer a reliable means of delivering gentamicin intramuscularly.     

Calculation of AQCmax: comparison of five ophthalmic fluoroquinolone solutions

ABSTRACT

Objective: Ocular tissue penetration of five different ophthalmic fluoroquinolone solutions in the rabbit eye was measured and evaluated by an index of the maximum aqueous concentration (AQCmax).

Methods: Moxifloxacin 0.5% (MFLX), levofloxacin 0.5% (LVFX), gatifloxacin 0.3% (GFLX), ofloxacin 0.3% (OFLX), or tosufloxacin tosilate 0.3% (TFLX) were instilled into the eyes of white rabbits every 15?min for a total of three doses. Aqueous humor, cornea, iris/ciliary body and vitreous body were collected 10 to 240?min after instillation and drug concentrations were measured by high-performance liquid chromatography.

Results: The concentration of MFLX was the highest in each tissue, with maximum concentrations of MFLX in the aqueous humor (10.16?±?1.59?µg/mL) at 30?min after instillation, cornea (156.07?±?95.97?µg/g) and iris/ciliary body (11.92?±?4.00?µg/g) at 10?min after instillation, and vitreous body (0.099?±?0.033?µg/mL) at 30?min after instillation. The concentration of TFLX was the lowest in each tissue, with LVFX, GFLX, and OFLX sharing the mid-ranks. AQCmax?:?MIC₉₀ ratio for S.?aureus was 150.67 for MFLX, 10.6 for LVFX, 9.69 for GFLX, 3.48 for OFLX, and could not be determined for TFLX.

Conclusion: AQCmax is a useful pharmacokinetic parameter for determining the therapeutic efficacy of an ophthalmic antibiotic, especially when combined with MIC₉₀ values for intraocular pathogens. C_max of MFLX ophthalmic solution was superior in all tissues (cornea, aqueous humor, iris/ciliary body and vitreous body) among the five ophthalmic solutions studied, exceeding the MIC₉₀ of S.?aureus in all tissues, and MIC₉₀s of S.?epidermidis, B.?cereus, and P.?acnes in aqueous humor, cornea, and iris/ciliary body. AQCmax was approximately proportional to C_max in iris/ciliary body and vitreous, and may be used in combination with MIC₉₀s as an index to predict the most appropriate dose and frequency of ophthalmic antibiotics in conjunction with other PK/PD parameters. This study may provide the groundwork for calculation of AQCmax in humans.     

Intraoperative corneal thickness measurements during corneal collagen cross-linking with isotonic riboflavin solution without dextran in corneal ectasia

Objective: To monitor the changes in corneal thickness during the corneal collagen cross-linking procedure by using isotonic riboflavin solution without dextran in ectatic corneal diseases.

Materials and Methods: The corneal thickness measurements were obtained before epithelial removal, after epithelial removal, following the instillation of isotonic riboflavin solution without dextran for 30?min, and after 10?min of ultraviolet A irradiation.

Results: Eleven eyes of eleven patients with progressive keratoconus (n?=?10) and iatrogenic corneal ectasia (n?=?1) were included in this study. The mean thinnest pachymetric measurements were 391.82?±?30.34?µm (320–434?µm) after de-epithelialization of the cornea, 435?±?21.17?µm (402–472?µm) following 30?min instillation of isotonic riboflavin solution without dextran and 431.73?±?20.64?µm (387–461?µm) following 10?min of ultraviolet A irradiation to the cornea.

Conclusion: Performing corneal cross-linking procedure with isotonic riboflavin solution without dextran might not induce corneal thinning but a little swelling throughout the procedure.     

Solid lipid micro-dispersions (SLMs) based on PEGylated solidified reverse micellar solutions (SRMS): a novel carrier system for gentamicin

Abstract

The purpose of this study was to formulate and evaluate novel PEGylated solidified reverse micellar solutions (SRMS)-based solid lipid microparticles (SLMs) for improved delivery of gentamicin. Lipid matrix (SRMS) [consisting of 15% w/w Phospholipon® 90G (P90G) in 35% w/w dika wax (Irvingia gabonensis) was formulated and characterized by differential scanning calorimetry (DSC). SLMs were formulated by melt-emulsification using the SRMS, PEG 4000 and gentamicin (1.0, 2.0, 3.0% w/w), and their physicochemical as well as pharmacokinetic parameters determined. In vitro permeation of gentamicin from the SLMs through artificial membrane (0.22?μm pore size) was carried out using Franz’s cell and phosphate-buffered saline (PBS, pH 7.4) as acceptor medium, while bioevaluation was performed using clinical isolates of Pseudomonas aeruginosa and Staphylococcus aureus. Stable and irregularly-shaped gentamicin-loaded SLMs of size range 34.49?±?2.56 to 53.52?±?3.09?µm were obtained. The SLMs showed sustained drug permeation and exhibited time-dependent and capacity-limited bioactivity. Overall, SLMs containing 2% w/w SRMS, 3% w/w gentamicin and PEG 4000 entrapped the highest amount of drug, gave highest IZD against the test organisms and highest permeation flux (5.239?μg/cm².min) and permeation coefficient (1.781?×?10^?6?cm/min) within 420?min, while pure gentamicin gave the least. Preliminary in vivo pharmacokinetic studies also showed an AUC-₂₄ of 1507?µg/h/ml for the optimized formulation, while that of oral drug solution was 678?µg/h/ml. This showed a 2.2-fold increase in the systemic bioavailability of gentamicin from the optimized formulation. PEGylated SRMS-based SLMs prepared with heterolipid from Irvingia gabonensis would likely offer a reliable delivery system for gentamicin.     

Diffusion loading and drug delivery characteristics of alginate gel microparticles produced by a novel impinging aerosols method

Microencapsulation of a hydrophilic active (gentamicin sulphate (GS)) and a hydrophobic non-steroidal anti-inflammatory drug (ibuprofen) in alginate gel microparticles was accomplished by molecular diffusion of the drug species into microparticles produced by impinging aerosols of alginate solution and CaCl₂ cross-linking solution. A mean particle size in the range of 30–50 µm was measured using laser light scattering and high drug loadings of around 35 and 29% weight/dry microparticle weight were obtained for GS and ibuprofen respectively. GS release was similar in simulated intestinal fluid (phosphate buffer saline (PBS), pH 7.4, 37°C) and simulated gastric fluid (SGF) (HCl, pH 1.2, 37°C) but was accelerated in PBS following incubation of microparticles in HCl. Ibuprofen release was restricted in SGF but occurred freely on transfer of microparticles into PBS with almost 100% efficiency. GS released in PBS over 7?h, following incubation of microparticles in HCl for 2?h was found to retain at least 80% activity against Staphylococcus epidermidis while Ibuprofen retained around 50% activity against Candida albicans. The impinging aerosols technique shows potential for producing alginate gel microparticles of utility for protection and controlled delivery of a range of therapeutic molecules.