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.     

Sustained-release diclofenac potassium-loaded solid lipid microparticle based on solidified reverse micellar solution: in vitro and in vivo evaluation

Objective: To formulate sustained-release diclofenac potassium-loaded solid lipid microparticles (SLMs) based on solidified reverse micellar solution (SRMS) and to evaluate the in vitro and in vivo properties.

Methods: SRMS consisting of mixtures of Phospholipon® 90H and Softisan® 154 were used to formulate diclofenac potassium-loaded SLMs. Characterization based on the particle size and morphology, stability and encapsulation efficiency (EE%) were carried out on the SLMs. In vitro release was carried out in simulated intestinal fluid (pH 7.5). Anti-inflammatory and ulcerogenic properties were studied using rats.

Results: Maximum EE% of 95%, 94% and 93% were obtained for SLMs formulated with SRMS 1:1, 2:1 and 1:2, respectively. In vitro release showed about 85–90% drug release at 13?h. Diclofenac potassium-loaded SLMs showed good anti-inflammatory and gastro-protective properties.

Conclusion: Diclofenac potassium-loaded SLMs based on SRMS could be used orally or parenterally under controlled conditions, for once daily administration.     

Ultrahigh verapamil-loaded controlled release polymeric beads using superamphiphobic substrate: D-optimal statistical design,in vitro and in vivo performance

Controlled-release multiparticulate systems of hydrophilic drugs usually suffer from poor encapsulation and rapid-release rate. In the present study, ultra-high loaded controlled release polymeric beads containing verapamil hydrochloride (VP) as hydrophilic model drug were efficiently prepared using superamphiphobic substrates aiming to improve patient compliance by reducing dosing frequency. Superamphiphobic substrates were fabricated using clean aluminum sheets etched with ammonia solution and were treated with 1.5% (w/v) perfluorodecyltriethoxysilane (PFDTS) alcoholic solution. The effect of the main polymer type (lactide/glycolide (PLGA) 5004A, PLGA 5010, and polycaprolactone (PCL)), copolymer (Eudragit RS100) content together with the effect of drug load on encapsulation efficiency (EE%) and in vitro drug release was statistically studied and optimized via D-optimal statistical design. In vivo pharmacokinetic study was carried out to compare the optimized system relative to the market product (Isoptin^®). Results revealed that superamphiphobic substrates were successfully prepared showing a rough micro-sized hierarchical structured surface upon observing with scanning electron microscope and were confirmed by high contact angles of 151.60?±?2.42 and 142.80°±05.23° for water and olive oil, respectively. The fabricated VP-loaded beads showed extremely high encapsulation efficiency exceeding 92.31% w/w. All the prepared systems exhibited a controlled release behavior with Q12?h ranging between 5.46 and 95.90%w/w. The optimized VP-loaded system composed of 150?mg (1.5% w/v) PCL without Eudragit RS100 together with 160?mg VP showed 2.7-folds mean residence time compared to the market product allowing once daily administration instead of three times per day.     

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.     

Formulation,in vitro and in vivo evaluation of halofantrine-loaded solid lipid microparticles

Abstract

Context: Formulation, characterization, in vitro and in vivo evaluation of halofantrine-loaded solid lipid microparticles (SLMs).

Objective: The objective of the study was to formulate and evaluate halofantrine-loaded SLMs.

Materials and methods: Formulations of halofantrine-loaded SLMs were prepared by hot homogenization and thereafter lyophilized and characterized using particle size, pH stability, loading capacity (LC) and encapsulation efficiency (EE). In vitro release of halofantrine (Hf) from the optimized SLMs was performed in SIF and SGF. In vivo study using Peter’s Four day suppressive protocol in mice and the mice thereafter subjected to histological studies in kidney and liver.

Results: Results obtained indicated that EE of 76.32% and 61.43% were obtained for the SLMs containing 7% and 3% of Hf respectively. The SLMs loaded with 3% of Hf had the highest yield of 73.33%. Time-dependent pH stability analysis showed little variations in pH ranging from 3.49?±?0.04 to 4.03?±?0.05.

Discussion: The SLMs showed pH-dependent release profile; in SIF (43.5% of the drug for each of H₂ and H₃) compared with SGF (13 and 18% for H₂ and H₃ respectively) after 8?h. The optimized SLMs formulation and Halfan® produced a percentage reduction in parasitemia of 72.96% and 85.71% respectively. The histological studies revealed that the SLMs formulations have no harmful effects on the kidney and liver.

Conclusion: SLMs formulations might be an alternative for patients with parasitemia as there were no harmful effects on vital organs of the mice.     

Formulation in vitro and in vivo evaluation of SRMS-based heterolipid-templated homolipid delivery system for diclofenac sodium

The sole objective of this work was to design successful dosage oral forms of diclofenac sodium (DiNa)-loaded solid lipid microparticles (SLM) based on solidified reverse micellar solution (SRMS). Hot homogenization technique was employed to prepare DicNa SLM using a mixture goat fat and Phospholipon® 90?G as lipid matrix and Tween®-80 as mobile surfactant. Characterization based on percentage yield, morphology, particle size, zeta potential, percentage encapsulation, pH and stability of SLMs were investigated. Anti-inflammatory, gastrointestinal tract (GIT) sparing effect and pharmacokinetics were carried out in rat model after oral administration. Results showed that the SLMs were spherical and smooth. The optimized formulation (SLM-4) had particle size of 79.40?±?0.31?µm, polydispersity index of 0.633?±?0.190, zeta potential of ?63.20?±?0.12?mV and encapsulation efficiency of 91.2?±?0.1% with good stability after 8?months of storage. The DicNa SLM had sustained release effect with good anti-inflammatory activity. Higher and prolonged plasma DicNa concentration was shown by the SLM-4 compared to pure drug and a conventional sample. These studies demonstrate that DicNa-loaded SLM based on SRMS could be a promising oral formulation for enhanced bioavailability, pharmacologic activity and gastrointestinal sparing effect of the NSAID, DicNa.     

Formulation and in vitro evaluation of a PEGylated microscopic lipospheres delivery system for ceftriaxone sodium

The aim of this study was to formulate and evaluate in vitro, ceftriaxone sodium lipospheres dispersions for oral administration. Ceftriaxone sodium lipospheres were prepared by melt-emulsification using 30%w/w Phospholipon^® 90H in Softisan^® 154 as the lipid matrix containing increasing quantities of PEG 4000 (10, 20, 30, and 40%w/w). Characterization based on particle size, particle morphology, encapsulation efficiency, loading capacity and pH were carried out on the lipospheres. Microbiological studies of the ceftriaxone sodium-loaded lipospheres were performed using Escherichia coli as the model organism. In vitro permeation of ceftriaxone sodium from the lipospheres through artificial membrane (0.22?μm pore size) was carried out using Franz cell and simulated intestinal fluid (SIF) without pancreatin as acceptor medium. Photomicrographs revealed spherical particles within a micrometer range with minimal growth after 1 month (Maximum size?=?64.76?±?3.81?μm). Microbiological studies indicated that lipospheres formulated with 20%w/w of PEG 4000 containing 2%w/w or 3%w/w of ceftriaxone sodium gave significantly (p?<?0.05) higher inhibition zone diameter than those with 30%w/w or 40%w/w of PEG 4000. The result also indicated that lipospheres with 10%w/w PEG 4000 resulted in significantly higher encapsulation efficiency (p?<?0.05) while those with 30%w/w gave the least, while the loading capacity values ranged from 3.22?mg of ceftriaxone sodium/100?mg of lipid to 6.36?mg of ceftriaxone sodium/100?mg of lipid. Permeation coefficient values varied and ranged from 8.55?×?10^?7 cm/s to 2.08?×?10^?6 cm/s depending on the concentration of PEG 4000. The result of this study gave insight that the issue of ceftriaxone stability in oral formulation could be adequately addressed by tactical engineering of lipid drug delivery systems such as lipospheres.     

Novel solidified reverse micellar solution-based mucoadhesive nano lipid gels encapsulating miconazole nitrate-loaded nanoparticles for improved treatment of oropharyngeal candidiasis

Objective: To develop and evaluate solidified-reverse-micellar-solution (SRMS)-based oromucosal nano lipid gels for improved localised delivery of miconazole nitrate (MN).

Methods: Phospholipon^® 90G and Softisan^® 154 (3:7) were used to prepare SRMS by fusion. Solid lipid nanoparticles (SLNs, 0.25–1.0% w/w MN) formulated with the SRMS by high shear homogenisation were employed to prepare mucoadhesive nano lipid gels. Physicochemical characterisation, drug release in simulated salivary fluid (SSF) (pH 6.8) and anti-candidal activity were carried out.

Results: The SLNs were spherical nanoparticles, had mean size of 133.8?±?6.4 to 393.2?±?14.5?nm, low polydispersity indices, good encapsulation efficiency (EE) (51.96?±?2.33–67.12?±?1.65%) and drug loading (DL) (19.05?±?2.44–24.93?±?1.98%). The nano lipid gels were stable, spreadable, pseudoplastic viscoelastic mucoadhesive systems that exhibited better prolonged release and anti-candidal properties than marketed formulation (Daktarin^® oral gel) (p?Conclusion: This study has shown that SRMS-based nano lipid gels could be employed to prolong localised oromucosal delivery of MN.     

Sustained release indomethacin-loaded solid lipid microparticles based on solidified reverse micellar solution (SRMS): in vitro and in vivo evaluation

Solidified reverse micellar solutions (SRMS) were formulated using phospholipid (Phospholipon 90H) and triglyceride (Softisan 154) in the ratios of 1:1, 2:1 and 1:2, respectively. SLMs were prepared by melt homogenization technique. Characterization based on yield, mean particle diameter and morphology, pH, thermal analysis and encapsulation efficiency (EE%) were carried out on the SLMs. In vitro release was carried out in simulated intestinal fluid (SIF, pH 7.5), while the anti-inflammatory and ulcerogenic properties were studied using rats. From the results, the mean particle diameter of SLMs ranged from 2.19 ± 0.05 μm to 20.77 ± 0.03 μm. Maximum EE% of 96, 93 and 94 % were obtained and showed significant variation within the batches (p < 0.05). The release profile of indomethacin-loaded SLMs showed about 82-99 % drug release at 13 h. Indomethacin-loaded SLMs showed good anti-inflammatory and gastro-protective effects, and could be formulated for once-daily administration, either orally or parenterally, under controlled conditions.     

Formulation and optimization of nanoemulsion using antifungal lipid and surfactant for accentuated topical delivery of Amphotericin B

The objective of the study was to develop, optimize and evaluate a nanoemulsion (NE) of Amphotericin B (AmB) using excipients with inherent antifungal activities (Candida albicans and Aspergillus niger) for topical delivery. AmB-loaded NE was prepared using Capmul PG8 (CPG8), labrasol and polyethylene glycol-400 by spontaneous titration method and evaluated for mean particle size, polydispersity index, zeta potential and zone of inhibition (ZOI). NE6 composed of CPG8 (15%w/w), S_mix (24%w/w) and water (61%w/w) was finally selected as optimized NE. AmB-NE6 was studied for improved in vitro release, ex vivo skin permeation and deposition using the Franz diffusion cell across the rat skin followed with drug penetration using confocal laser scanning microscopy (CLSM) as compared to drug solution (DS) and commercial Fungisome^®. The results of in vitro studies exhibited the maximum ZOI value of NE6 as 19.1?±?1.4 and 22.8?±?2.0?mm against A. niger and C. albicans, respectively, along with desired globular size (49.5?±?1.5?nm), zeta potential (?24.59?mV) and spherical morphology. AmB-NE6 revealed slow and sustained release of AmB as compared to DS in buffer solution (pH 7.4). Furthermore, AmB-NE6 elicited the highest flux rate (22.88?±?1.7?μg/cm²/h) as compared to DS (2.7?±?0.02?μg/cm²/h) and Fungisome^® (11.5?±?1.0?μg/cm²/h). Moreover, the enhancement ratio and drug deposition were found to be highest in AmB-NE6 than DS across the stratum corneum barrier. Finally, CLSM results corroborated enhanced penetration of the AmB-NE6 across the skin as compared to Fungisome^® and DS suggesting an efficient, stable and sustained topical delivery.     

Formulation of novel sustained release rifampicin-loaded solid lipid microparticles based on structured lipid matrices from Moringa oleifera

Abstract

Objectives: To formulate sustained release rifampicin-loaded solid lipid microparticles (SLMs) using structured lipid matrices based on Moringa oil (MO) and Phospholipon 90G (P90G).

Methods: Rifampicin-loaded and unloaded SLMs were formulated by melt homogenization and characterized in terms of particle morphology and size, percentage drug content (PDC), pH stability, stability in simulated gastric fluid (SGF, pH 1.2), minimum inhibitory concentration (MIC) and in vitro release. In vivo release was studied in Wistar rats.

Results: Rifampicin-loaded SLMs had particle size range of 32.50?±?2.10 to 34.0?±?8.40?μm, highest PDC of 87.6% and showed stable pH. SLMs had good sustained release properties with about 77.1% release at 12?h in phosphate buffer (pH 6.8) and 80.3% drug release at 12?h in simulated intestinal fluid (SIF, pH 7.4). SLMs exhibited 48.51% degradation of rifampicin in SGF at 3?h, while rifampicin pure sample had 95.5% degradation. Formulations exhibited MIC range of 0.781 to 1.562, 31.25 to 62.5 and 6.25 to 12.5?μg/ml against Salmonella typhi, Escherichia coli, and Bacillus subtilis respectively and had higher in vivo absorption than the reference rifampicin (p?<?0.05).

Conclusion: Rifampicin-loaded SLMs could be used once daily for the treatment tuberculosis.     

Polyamidoamine (PAMAM) dendrimers as potential release modulators and oral bioavailability enhancers of vardenafil hydrochloride

Vardenafil hydrochloride (VAR) is an erectile dysfunction treating drug. VAR has a short elimination half-life (4–5?h) and suffers low oral bioavailability (15%). This work aimed to explore the dual potential of VAR-dendrimer complexes as drug release modulators and oral bioavailability enhancers. VAR-dendrimer complexes were prepared by solvent evaporation technique using four dendrimer generations (G4.5, G5, G5.5 and G6) at three concentrations (190?nM, 380?nM and 950?nM). The systems were evaluated for intermolecular interactions, particle size, zeta potential, drug entrapment efficiency percentages (EE%) and drug released percentages after 2?h (Q_2h) and 24?h (Q_24h). The results were statistically analyzed, and the system showing the highest desirability was selected for further pharmacokinetic studies in rabbits, in comparison to Levitra^® tablets. The highest desirability (0.82) was achieved with D10 system comprising VAR (10?mg) and G6 (190?nM). It possessed small particle size (113.85?nm), low PDI (0.19), positive zeta potential (+21.53), high EE% (75.24%), promising Q_2?h (41.45%) and Q_24?h (74.05%). Compared to Levitra^® tablets, the significantly (p?<?0.01) delayed T_max, prolonged MRT_(0?∞) and higher relative bioavailability (3.7-fold) could clarify the dual potential of D10 as a sustained release system capable of enhancing VAR oral bioavailability.     

Sustained ocular delivery of Dorzolamide-HCl via proniosomal gel formulation: in-vitro characterization,statistical optimization,and in-vivo pharmacodynamic evaluation in rabbits

Glaucoma is the second cause of blindness worldwide. Frequent administration of traditional topical dosage forms may lead to patient incompliance and failure of treatment. Our study aims to formulate proniosomal gel formulations that sustain the release of the water-soluble anti-glaucoma drug Dorzolamide-HCl (Dorz). Proniosomal gel formulations were prepared using coacervation phase separation method according to a 5² full factorial design. The effects of Cholesterol and surfactant (Span 40) amounts (independent variables) on the percentage entrapment efficiency (EE%), particle size (PS), and the percent of drug released after 8?h (Q8h) (dependent variables (DVs)) were investigated. An optimized formulation (OF) was chosen based on maximizing EE% and Q8h and minimizing PS. An intraocular pressure (IOP) pharmacodynamic study was performed in rabbits to evaluate the in-vivo performance of the OF-gel compared to the marketed Trusopt^® eye drops. The results showed that the independent variables studied significantly affected EE%, PS, and Q8h. OF was the one containing 60?mg Cholesterol and 540?mg Span 40. It had desirability of 0.885 and its actually measured DVs deviated from the predicted ones by a maximum of 4.8%. The in-vivo pharmacodynamic study showed that OF could result in higher reduction in IOP, significantly sustain that reduction in IOP and increase Dorz bioavailability compared to Trusopt^® eye drops. Thus the OF-gel is very promising for being used in glaucoma treatment.     

Fabrication of long-acting insulin formulation based on poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanoparticles: preparation,optimization, characterization,and in vitro evaluation

The purpose of this research was the fabrication, statistical optimization, and in vitro characterization of insulin-loaded poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) nanoparticles (INS-PHBV-NPs). Nanopar-ticles were successfully developed by double emulsification solvent evaporation method. The NPs were characterized for particle size, entrapment efficiency (EE%), and polydispersity index (PDI). The NPs also were characterized by scanning electron microscopy (SEM), Fourier transformed infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and circular dichroism (CD). The optimum conditions were found to be 1.6% polyvinyl alcohol (PVA), 0.9% of PHBV, and 15?mg/ml of insulin with the aid of the Box–Behnken experimental design results. The optimized NPs showed spherical shape with particle size of 250.21?±?11.37?nm, PDI of 0.12?±?0.01, and with EE% of 90.12?±?2.10%. In vitro drug release pattern followed Korsmeyer–Peppas model and exhibited an initial burst release of 19% with extended drug release of 63.2% from optimized NPs within 27?d. In conclusion, these results suggest that INS-PHBV-NPs could be a promising candidate for designing an injectable sustained release formulation for insulin.     

Improved oral absorption and anti-lung cancer activity of paclitaxel-loaded mixed micelles

The aim of this study was to establish a paclitaxel (PTX)-loaded mixed micelle delivery system (PTX-TP-M) with vitamin E-TPGS (TPGS) and Plasdone®S-630 Copovidone (PVPS630) as carriers to improve the solubility, oral absorption, and anti-tumor activity of PTX against lung cancer. In this study, PTX-TP-M was prepared using the ethanol thin-film dispersion method followed by characterization of the binary mixed micelles system. The average size of the PTX-TP-M was 83.5?±?1.8?nm with a polydispersity index of 0.265?±?0.007 and the drug loading (DL%) and entrapment efficiency (EE%) were 3.09?±?0.09% and 95.67?±?2.84%, respectively, which contributed to a high solubility of PTX about 24947-fold increase in water (4.78?±?0.14?mg/mL). In addition, TEM analysis showed that the PTX-TP-M appeared spherical in structure and was well dispersed without aggregation and adhesion. In vitro release studies showed that the PTX-TP-M displayed a sustained release compared to free PTX in the dialysis bag. The efflux ratio of PTX reduced from 44.83 to 3.52 when formulated as PTX-TP-M; a 92.15% reduction, studied using the Caco-2 monolayer model. The oral bioavailability of PTX also improved by 4.35-fold, suggesting that PTX-TP-M can markedly promote the absorption in the gastrointestinal tract. Using in vitro MTT assays, it was observed that cytotoxicity was markedly increased, and IC₅₀ values of PTX-TP-M (3.14?±?0.85 and 8.28?±?1.02?μg/mL) were lower than those of PTX solution (5.21?±?0.93 and 14.53?±?1.96?μg/mL) in A549 and Lewis cell, respectively. In vivo anti-tumor studies showed that PTX-TP-M achieved higher anti-tumor efficacy compared with PTX in Lewis bared C57BL/6 mice. Furthermore, a gastrointestinal safety assay also proved the safety of PTX-TP-M. All results demonstrated that the PTX-TP-M exhibited great potential for delivering PTX with increased solubility, oral bioavailability, and anti-cancer activity and this binary mixed micelles drug delivery system has potential to be used clinically.     

Preparation and testing of cefquinome-loaded poly lactic-co-glycolic acid microspheres for lung targeting

The aim of this study was to prepare cefquinome-loaded poly lactic-co-glycolic acid (PLGA) microspheres and to evaluate their in vitro and in vivo characteristics. Microspheres were prepared using a spry drier and were characterized in terms of morphology, size, drug-loading coefficient, encapsulation ratio and in vitro release. The prepared microspheres were spherical with smooth surfaces and uniform size (12.4?±?1.2?μm). The encapsulation efficiency and drug loading of cefquinome was 91.6?±?2.6 and 18.3?±?1.3%, respectively. In vitro release of cefquinome from the microspheres was sustained for 36?h. In vivo studies identified the lung as the target tissue and the region of maximum cefquinome release. A partial lung inflammation was observed but disappeared spontaneously as the microspheres were removed through in vivo decay. The sustained cefquinome release from the microspheres revealed its applicability as a drug delivery system that minimized exposure to healthy tissues while increasing the accumulation of therapeutic drug at the target site. These results indicated that the spray-drying method of loading cefquinome into PLGA microspheres is a straightforward method for lung targeting in animals.     

Theophylline colon specific tablets for chronotherapeutic treatment of nocturnal asthma

The ultimate goal is to design a new chronotherapeutic system for theophylline (TPH) with high potential benefits in treating nocturnal asthma. TPH core tablets were prepared by wet granulation using a developed formula. Compression coating over core tablets containing 200?mg TPH was done using granulated chitosan with 10% PVP K30. Different formulae F1, F2 and F3 were prepared using coat weights 260, 300 and 360?mg, respectively. The in vitro release characteristics in both variant pH media mimicking the gastrointestinal media and in media containing rat cecal content were monitored. The in vivo performance of the optimum formula was compared with Avolen^® SR in Beagle dogs. F3 with high coat thickness exhibited a minimal release after 5-h release study. Both F2 and F3 showed more than 50% drug release after 4?h in the rat cecal medium. This reflects the colon selectivity of the system. The C_max values were found to be 5.49?±?0.46 and 5.12?±?0.85?μg/mL for F3 and Avolen^® SR, respectively, F3 showed higher mean plasma concentration than Avolen^® SR from the beginning and continued till 7?h post administration indicating high potential as chronotherapeutic treatment of nocturnal asthma.     

Salmon calcitonin-loaded Eudragit® and Eudragit®-PLGA nanoparticles: in vitro and in vivo evaluation

The main objective of this study was to prepare salmon calcitonin (sCT)-loaded Eudragit®RSPO, Eudragit®L100 and Eudragit®-poly(lactic-co-glycolic acid) blend nanoparticles for in vitro and in vivo evaluation as an oral drug delivery system. The prepared nanoparticles ranged in size from 179.7 to 308.9?nm with a polydispersity index between 0.051 and 2.75, and had surface charges ? ?11 to +6?mV. Efficient sCT encapsulation and release was observed with all the nanoparticle formulations. The polymer type was an important factor that influenced the release characteristics and the in vivo hypocalcemic effect. Nanoparticle formulations were also prepared with sodium taurodeoxycholate (NaTDC) and characterized. No statistically significant difference was noted between the hypocalcemic effect of any of the nanoparticle formulations with and without NaTDC (p?>?0.05). The use of Eudragit®RSPO nanoparticles appears to be a potential approach for the oral delivery of sCT.     

Development and evaluation of co-formulated docetaxel and curcumin biodegradable nanoparticles for parenteral administration

Context: Technology for development of biodegradable nanoparticles encapsulating combinations for enhanced efficacy.

Objective: To develop docetaxel (DTX) and curcumin (CRM) co-encapsulated biodegradable nanoparticles for parenteral administration with potential for prolonged release and decreased toxicity.

Materials and methods: Modified emulsion solvent-evaporation technique was employed in the preparation of the nanoparticles optimized by the face centered-central composite design (FC-CCD). The uptake potential was studied in MCF-7 cells, while the toxicity was evaluated by in vitro hemolysis test. In vivo pharmacokinetic was evaluated in male Wistar rats.

Results and discussion: Co-encapsulated nanoparticles were developed of 219?nm size, 0.154 PDI, ?13.74?mV zeta potential and 67.02% entrapment efficiency. Efficient uptake was observed by the nanoparticles in MCF-7 cells with decreased toxicity in comparison with the commercial DTX intravenous injection, Taxotere®. The nanoparticles exhibited biphasic release with initial burst release followed by sustained release for 5 days. The nanoparticles displayed a 4.3-fold increase in AUC (391.10?±?32.94 versus 89.77?±?10.58?μg/ml min) in comparison to Taxotere® with a 6.2-fold increase in MRT (24.78?±?2.36 versus 3.58?±?0.21?h).

Conclusion: The nanoparticles exhibited increased uptake, prolonged in vitro and in vivo release, with decreased toxicity thus exhibiting potential for enhanced efficacy.     

Solid lipid microparticles: An approach for improving oral bioavailability of aspirin

The objectives of the work were to develop a lipid based delivery system for aspirin and to evaluate its physicochemical and pharmacodynamic properties. Aspirin-loaded solid lipid microparticles (SLMs) were formulated by hot homogenization and analysed for their encapsulation efficiency (EE%), in vitro release, particle size, anti-inflammatory and ulcer inhibition properties. Particle size ranged from 33.10 ± 5.85 to 43.50 ± 7.27 µm for batches A1 to A3 SLMs loaded with 1, 3 and 5% aspirin and containing Poloxamer 407, while batches B1, B2 and B3 formulated with Soluplus as surfactant had particle size range of 31.10 ± 1.46 to 45.60 ± 2.92 µm. Batches A1 and B1 containing 1% of aspirin had the highest EE of 70 and 72% respectively. Maximum in vitro release of 95.1 and 93.2% were obtained at 8 h from batches A1 and B1 respectively. SLMs exhibited about 77.8% oedema inhibition, while the reference had 66.7% and ulcer inhibition range of 25–75%. Aspirin-loaded SLMs exhibited good properties and could be used orally twice daily for the treatment of inflammation.