Stability and degradation kinetics of etoposide-loaded parenteral lipid emulsion

Etoposide was incorporated in lipid emulsion to develop an i.v. formulation, and improve its physical and chemical stability without addition of organic solvents, for use as a commercial formulation. High-pressure homogenization was used to prepare the lipid nanospheres and localize the drug at the surfactant layer. The particle size distribution and zeta potential were measured using photon correlation spectroscopy (PCS). Ultrafiltration was used to estimate the relative percentage of etoposide in each phase. The stability profile of etoposide in the lipid emulsion at various temperatures, pH values, and concentrations of drug was monitored by high performance liquid chromatography (HPLC). The degradation pattern of etoposide in lipid emulsion followed pseudo-first-order kinetics. The shelf life (T(90%)) of etoposide in lipid emulsion was estimated to be 47 days at 25 degrees C and it would be stable when stored for 427 days at 4 degrees C, which is a significant improvement compared with a stability of 9.5 days in aqueous solution at 25 degrees C. Etoposide in lipid emulsion and aqueous solution were both most stable at pH 5.0 with a half-life of 54.7 h and 38.6 min at 80 degrees C, respectively. The hydrolysis kinetics of etoposide in lipid emulsion was also shown to be dependent on the drug concentration.     

Preparation and characterization of n-dodecyl-ferulate-loaded solid lipid nanoparticles (SLN)

Solid lipid nanoparticles (SLN) containing a novel potential sunscreen n-dodecyl-ferulate (ester of ferulic acid) were developed. The preparation and stability parameters of n-dodecyl-ferulate-loaded SLN have been investigated concerning particle size, surface electrical charge (zeta potential) and matrix crystallinity. The chemical stability of n-dodecyl-ferulate at high temperatures was also assessed by thermal gravimetry analysis. For the selection of the appropriated lipid matrix, chemically different lipids were melted with 4% (m/m) of active and lipid nanoparticles were prepared by the so-called high pressure homogenization technique. n-Dodecyl-ferulate-loaded SLN prepared with cetyl palmitate showed the lowest mean particle size and polydispersity index, as well as the highest physical stability during storage time of 21 days at 4, 20 and 40 degrees C. These colloidal dispersions containing the sunscreen also exhibited the common melting behaviour of aqueous SLN dispersions.     

Radiation sterilisation of doxorubicin bound to poly(butyl cyanoacrylate) nanoparticles

Doxorubicin-loaded poly(butyl cyanoacrylate) (PBCA) nanoparticles were prepared by anionic polymerisation under non-aseptic conditions. The feasibility of sterilisation of this formulation using either gamma-irradiation or electron beam irradiation was investigated. The irradiation doses ranged from 10 to 35 kGy. Bacillus pumilus was used as the official test microorganism. The bioburden of the untreated formulation was found to be 100 CFU/g. Microbiological monitoring revealed that at this level of the bioburden the irradiation dose of 15 kGy was sufficient for sterilisation of the nanoparticles. The formulation showed excellent stability with both types of irradiation in the investigated dose range. The irradiation did not influence the physicochemical parameters of the drug-loaded and empty nanoparticles, such as the mean particle size, polydispersity, and aggregation stability. The molecular weights of the PBCA polymer as well as the polydispersity indices (M(w)/M(n)) remained nearly unchanged. The drug substance was stable to radiolysis. Additionally, the presence of irradiation-induced radicals was evaluated by ESR spectroscopy after storage of the particles at ambient temperature. The paramagnetic species found in the formulation were mainly produced by irradiation of mannitol and dextran used as excipients.     

Development and characterization of PLGA nanospheres and nanocapsules containing xanthone and 3-methoxyxanthone.

The aim of the present work was to develop and characterize two different nanosystems, nanospheres and nanocapsules, containing either xanthone (XAN) or 3-methoxyxanthone (3-MeOXAN), with the final goal of improving the delivery of these poorly water-soluble compounds. The xanthones-loaded nanospheres (nanomatrix systems) and nanocapsules (nanoreservoir systems), made of poly(DL-lactide-co-glycolide) (PLGA), were prepared by the solvent displacement technique. The following characteristics of nanoparticle formulations were determined: particle size and morphology, zeta potential, incorporation efficiency, thermal behaviour, in vitro release profiles and physical stability at 4 degrees C. The nanospheres had a mean diameter <170 nm, a narrow size distribution (polydispersity index <0.1), and a negative surface charge (zeta potential <-36 mV). Their incorporation efficiencies were 33% for XAN and 42% for 3-MeOXAN. The presence of the xanthones did not affect the nanospheres size and zeta potential. DSC studies indicated that XAN and 3-MeOXAN were dispersed at a molecular level within the polymeric nanomatrix. Nanocapsules were also nanometric (mean size <300 nm) and exhibited a negative charge (zeta potential <-36 mV). Their incorporation efficiency values (>77%) were higher than those corresponding to nanospheres for both xanthones. The release of 3-MeOXAN from nanocapsules was similar to that observed for the correspondent nanoemulsion, indicating that drug release is mainly governed by its partition between the oil core and the external aqueous medium. In contrast, the release of XAN from nanocapsules was significantly slower than from the nanoemulsion, a behaviour that suggests an interaction of the drug with the polymer. Nanocapsule formulations exhibited good physical stability at 4 degrees C during a 4-month period for XAN and during a 3-month period for 3-MeOXAN.     

Studies on the effect of pilocarpine incorporation into a submicron emulsion on the stability of the drug and the vehicle.

In order to obtain a novel ocular formulation with a potential for prolonging pilocarpine activity, the drug (2.0%) was incorporated into a submicron emulsion containing soya-bean oil and lecithin as emulgator. The effect of drug incorporation into the emulsion on its physical stability and on the other hand, the potential of the vehicle to reduce drug degradation at pH higher than 5.0 was studied. The pH was adjusted to 6.5 or 5.0 and the physicochemical stability of the formulations was observed. The mean diameter of oily particles in the resulting emulsions measured by a laser diffractometer was 0.6-0.7 micron and this was larger than in a drug-free emulsion where a 0.33 micron value was measured. The formulations were physically stable for 6 months at 4 degrees C, but progressing chemical degradation of pilocarpine was noted at pH 6.5. At that pH nearly 8% of pilocarpine was degraded to isopilocarpine and pilocarpic acid, both in the emulsion and in the solution. Thus, it may be concluded that pilocarpine in submicron emulsion is not protected against degradation. The presence of pilocarpine changes the physical stability of the vehicle since the formulation was easily destabilized during autoclaving or at room temperature. In the presence of higher concentration of lecithin (2.4%) or co-emulgators (poloxamer 2.0% or Tween 80 0.5%) the mean droplet size in the emulsions was the same as in a drug-free system. However the emulsions containing poloxamer were not stable during storage. Viscosity of pilocarpine emulsions can be increased by addition of methylcellulose or sodium carmellose (1.0%), but an intensive creaming occurs in these systems. Pilocarpine base is less suitable for emulsion preparation than hydrochloride salt, and emulsions prepared at pH 5.0 show the most satisfying stability.     

pH dependent effect of glycosylation on protein stability.

The effect of glycosylation state on the thermal and storage stability of interleukin-2 mutein (IL-2 mutein) was investigated. The thermal stability of IL-2 mutein was studied by DSC and UV. An accelerated storage stability study was conducted at 40 degrees C in the dark and analyzed by UV, SDS-PAGE, and RP-HPLC. The unfolding temperatures (Tu) of both glycosylated and unglycosylated forms of IL-2 mutein are similar (within +/-1 degrees C) at pH 5.5 and 7.5. At pH 4.0, the Tu of glycosylated IL-2 mutein was 4 degrees C lower than that of the unglycosylated form. The precipitation temperature of glycosylated IL-2 mutein is similar to that of the unglycosylated form at pH 5.5 but 4 degrees C higher at pH 7.5. The precipitation temperature is not detectable for both forms at pH 4.0. During storage, both glycosylated and unglycosylated IL-2 mutein form aggregates (soluble and insoluble) and other degradation products. The aggregates are formed by both physical and chemical mechanisms. The major pathway of chemical aggregation appears to be disulfide bond formation/exchange. The glycosylated form is much less stable than the unglycosylated form at pH 4.0 and both forms are most stable at pH 5.5 in terms of thermal stability, precipitation rate and total degradation rate. This study clearly demonstrates that the effect of glycosylation on the stability of a protein is pH-dependent.     

注射用克拉霉素乳剂稳定性及影响因素考察

目的考察克拉霉素乳剂稳定性及其影响因素。方法以乳剂粒径,pH值变化和药物含量作为指标,考察了不同温度对克拉霉素乳剂稳定性的影响。结果乳剂在低温保存时稳定性良好,温度升高会显著影响乳剂稳定性,导致粒径增大和pH降低。根据Arrhenius公式求得储存温度为5℃时,T0.9=9.06年,长期稳定性试验结果表明,载药乳剂在12个月理化性质稳定。结论低温保存有利于提高该乳剂的稳定性。     

Prednisolone-loaded albumin nanospheres: in vitro and in vivo evaluation studies

Prednisolone-loaded bovine serum albumin (BSA) nanospheres prepared by pH-coacervation were evaluated regarding recovery, drug entrapment efficiency, particle size, shape, surface morphology, in vitro drug release profile, and in vivo distribution. The method of analysis was validated in terms of accuracy, precision, and repeatability. No significant change in the drug's chemical integrity was observed when incorporated in the nanospheres. It was observed that the average particle size and drug entrapment efficiency of the nanospheres increased with the increase in drug loading. All the batches exhibited biphasic drug release with an initial burst effect followed by gradual steady release. The higher the drug loading, the greater was the burst effect. The mechanism of prednisolone release from the nanospheres was found to be due to diffusion and erosion as observed by fitting the release data in different models. The drug's in vivo distribution was found to be highest in the liver followed by the spleen and lungs. Stability studies indicated that nanosphere formulations should be stored at 4 +/- 2 degrees C.     

Development of ascorbyl palmitate nanocrystals applying the nanosuspension technology

Ascorbyl palmitate (AP) is an antioxidant used in both cosmetics and food industry. Owing to its poor solubility and instability caused by oxidation having been observed in several colloidal systems, the aim of this study was to investigate the feasibility of applying the nanosuspension technology by high-pressure homogenization (HPH) (DissoCubes) technology) to enhance the chemical stability of AP, followed by lyophilization. Sodium dodecyl sulfate (SDS) and Tween 80 were chosen as emulsifying agents to stabilize the developed AP nanosuspensions. After 3 months of storage at three different temperatures (4 degrees C, 25 degrees C and 40 degrees C), the photon correlation spectroscopy (PCS) analysis of AP nanosuspensions revealed that the mean particle size of those stabilized with SDS significantly increased compared to those stabilized with Tween 80. The results observed from both atomic force microscopy (AFM) and scanning electron microscopy (SEM) revealed AP nanocrystals of cubic-like shape. The percentage of AP remaining in nanosuspensions stabilized with Tween 80 was higher than 90% after 3 months storage at 4 degrees C, 25 degrees C and 40 degrees C. To increase the chemical stability of AP nanosuspensions, a drug powder was prepared by lyophilization. The effect of the presence of cryoprotectant trehalose on the physical stability was evaluated at different concentrations. After redispersing the lyophilized product, the mean size of AP nanosuspensions without trehalose was significantly higher compared with the system with trehalose. After 3 months of storage at 25 degrees C the mean size of lyophilized AP nanosuspensions remained constant. X-ray diffraction revealed the crystalline character of AP nanocrystals after HPH and lyophilization.     

Molecular weights of poly(butyl cyanoacrylate) nanoparticles determined by mass spectrometry and size exclusion chromatography

Matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS) and size exclusion chromatography (SEC) were employed to elucidate the chemical composition, mean number average molecular weight (M_n), mean weight average molecular weight (M_w), and polydispersity (PD) of poly(butyl cyanoacrylate) (PBCA) manufactured by emulsion polymerisation. Both methods gave similar results for M_n, but substantial differences were observed for M_w and PD, with MALDI producing consistently lower values which could not be improved by off-line coupling of SEC and MALDI. MALDI gave a more detailed view on the chemical composition of the cyanoacrylate and revealed the presence of two additional polymer series with different end groups besides the expected PBCA series, which showed different retention in SEC. Their formation is explained by the secession/addition of formaldehyde from/to the regular polymer via (reverse) Knoevenagel reaction. In additional experiments, the influence of different pH on PBCA-NP during polymerisation was examined by comparison of polymerisation yield and particle diameter to their chemical composition as revealed by the MALDI spectra. The most uniform nanoparticles, with the highest polymerisation yield, narrowest particle size, and mass distribution were produced at pH 1.     

Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for application of ascorbyl palmitate

The aim of this study was to improve the chemical stability of ascorbyl palmitate (AP) in a colloidal lipid carrier for its topical use. For this purpose, AP-loaded solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and for comparison, a nanoemulsion (NE) were prepared employing the high pressure homogenization technique and stored at room temperature (RT), 4 degrees C and 40 degrees C. During 3 months, physical stability of these formulations compared to placebo formulations which were prepared by the same production method, was studied including recrystallization behaviour of the lipid with differential scanning calorimetry (DSC), particle size distribution and storage stability with photon correlation spectroscopy (PCS) and laser diffractometry (LD). After evaluating data indicating excellent physical stability, AP-loaded SLN, NLC and NE were incorporated into a hydrogel by the same production method as the next step. Degradation of AP by HPLC and physical stability in the same manner were investigated at the same storage temperatures during 3 months. As a result, AP was found most stable in both the NLC and SLN stored at 4 degrees C (p > 0.05) indicating the importance of storage temperature. Nondegraded AP content in NLC, SLN and NE was found to be 71.1% +/- 1.4, 67.6% +/- 2.9 and 55.2% +/- 0.3 after 3 months, respectively. Highest degradation was observed with NE at all the storage temperatures indicating even importance of the carrier structure.     

Physicochemical stability of high indomethacin payload ordered mesoporous silica MCM-41 and SBA-15 microparticles

Stability of high indomethacin (IMC) content formulations based on ordered mesoporous silica MCM-41 and SBA-15 materials was studied before and after a 3 month storage in stressed conditions (30 °C/56% RH). Overall, the physical stability of the samples was found satisfactory after the storage. However, some issues with the chemical stability were noted, especially with the MCM-41 based samples. The stability issues were evident from the decreased HPLC loading degrees of the drug after stressing as well as from the observed extra peaks in the HPLC chromatograms of the drug in the stressed samples. Drug release from the mesoporous formulations before stressing was rapid at pH 1.2 in comparison to bulk crystalline IMC. The release profiles also remained similar after stressing. Even faster and close to complete IMC release was achieved when the pH was raised from 1.2 to 6.8. To our knowledge, this is the first report of chemical stability issues of drugs in mesoporous silica drug formulations. The present results encourage further study of the factors affecting the chemical stability of drugs in mesoporous silica MCM-41 and SBA-15 formulations in order to realize their potential in oral drug delivery.     

Ocular tolerability and in vivo bioavailability of poly(ethylene glycol) (PEG)-coated polyethyl-2-cyanoacrylate nanosphere-encapsulated acyclovir

Acyclovir-loaded polyethyl-2-cyanoacrylate (PECA) nanospheres were prepared by an emulsion polymerization process in the micellar phase and characterized. The influence of the presence of nonionic surfactant as well as other substances [i.e., 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) and poly(ethylene glycol) (PEG)], on formulation parameters and loading capacity was investigated. In particular, the presence of PEG resulted in an increase of mean size and size distribution. To obtain PEG-coated PECA nanospheres with a mean size of < 200 nm, Pluronic F68 at concentrations > 1.5% (w/v) should be used during preparation. The presence of PEG also resulted in a change in zeta potential, from -25.9 mV for uncoated nanospheres to -12.2 mV for PEG-coated PECA nanospheres. The presence of HP-beta-CyD elicited an increase of nanosphere size and size distribution, but zeta potential was not influenced. In vitro drug release from nanospheres was determined in both phosphate buffer (pH 7.4) and plasma. The presence of HP-beta-CyD and PEG did not influence the acyclovir release rate in plasma. In the case of release in phosphate buffer, PEG-coated nanospheres showed a slower release. Ocular tolerability of PEG-coated PECA nanospheres was evaluated by the in vivo Draize test. This colloidal carrier was well tolerated, eliciting no particular inflammation at the level of the various ocular structures. In vivo ocular bioavailability was evaluated by instilling 50 microL of the acyclovir-loaded nanospheres only once in the conjunctival sac of rabbit eyes. At various time intervals, aqueous humour acyclovir content was determined by high-performance liquid chromatography. Acyclovir-loaded PEG-coated PECA nanospheres were compared with an aqueous solution of the drug and a physical mixture of acyclovir nanospheres. The acyclovir-loaded PEG-coated PECA nanospheres showed a significant (p < 0.001) increase of drug levels (25-fold) in aqueous humor compared with the free drug or the physical mixture. This finding is probably due to an improved ocular mucoadhesion of PEG-coated PECA nanospheres.     

Physical and chemical stability of miconazole liposomes prepared by supercritical aerosol solvent extraction system (ASES) process

The aerosol solvent extraction system (ASES) process was applied to prepare miconazole (MCZ) liposomes in a dry and reconstitutable form, the optimized temperature and pressure of which were 35 degrees C and 8.0 MPa, respectively. The influence of compositions of phosphatidylcholine (PC), cholesterol (CHOL), and poloxamer 407 (POLOX) as well as the pH of hydration medium on physical and chemical stability of both dry microparticles and liposomes hydrated from them were examined following storage at 4 degrees C and 25 degrees C for 3 months. MCZ microparticles in dry powder were stable on storage at 4 degrees C but degraded considerably after storage at 25 degrees C. MCZ liposomes hydrated from dry ASES-prepared microparticles at pH 4.0 tended to aggregate, whereas those hydrated at pH 7.2 tended to reduce in size on storage, especially with the addition of CHOL. Liposomes with high MCZ content stored at 4 degrees C degraded faster than when stored at 25 degrees C. Addition of POLOX tended to retard the degradation of MCZ liposomes, whereas CHOL appeared to enhance the degradation on storage under both conditions. The chemical degradation of MCZ liposomes appeared to follow the acid-catalyzed hydrolysis. The MCZ liposomes prepared by the ASES process in this study were substantially internalized after being incubated with human lymphocytes.     

Influence of formulation technique for hydroxypropyl-beta-cyclodextrin on the stability of aspirin in HFA 134a.

The objective of this study was to determine the influence of the formulation technique for 2-hydroxypropyl-beta-cyclodextrin (HP beta CD) on the stability of aspirin in a suspension-based pressurized metered-dose inhaler (pMDI) formulation containing a hydrofluoroalkane (HFA) propellant. HP beta CD was formulated in a pMDI as a lyophilized inclusion complex or a physical mixture with aspirin. A pMDI formulation containing aspirin alone was used as the control. The chemical stability of aspirin in each pMDI formulation was determined over 6-months storage at 5, 25 and 40 degrees C. The quantity of water taken up into the pMDI canister was determined by Karl Fisher titration after storage for 6 months. Differential scanning calorimetry (DSC) was used to confirm the formation of a complex between HP beta CD and aspirin. Aspirin in the lyophilized inclusion complex exhibited the most significant degree of degradation during the 6-months storage, while aspirin alone in the pMDI demonstrated a moderate degree of degradation. Aspirin formulated in the physical mixture displayed the least degree of degradation. The water uptake study showed that water ingress occurred to the greatest extent for formulations containing aspirin and HP beta CD physical mixture, and to the least extent for formulations containing aspirin alone. Finally, the DSC study indicated that an inclusion complex was formed in situ in the pMDI formulations containing the HP beta CD and aspirin physical mixture. In conclusion, HP beta CD may be used to enhance the stability of a chemically labile drug, but the drug stability may be affected by the method of preparation of the formulation.     

Hydrophilic gels containing chlorophyllin-loaded liposomes: development and stability evaluation

The aim of this study was to develop and characterize hydrophilic gels containing chlorophyllin(CHL)-loaded liposomes as well as to evaluate their stability. Two different CHL-loaded liposome dispersions using non-hydrogenated and hydrogenated soybean lecithin were prepared, characterized for their particle size, polydispersity index and trapping efficiency and incorporated in Carbopol 940 NF hydrogel. The gels obtained were analyzed for flow properties, pH values and CHL content. The control liposome-free gel was obtained by incorporating the CHL solution in the hydrogel. The stability of the gels was evaluated in terms of rheological properties, pH values and CHL content during 6 months' storage at 20 +/- 2 degrees C. Suitable gel formulations for topical use were obtained revealing shear-thinning plastic flow behaviour without significant thixotropy during the whole period of examination. High yield values of the samples during the whole period indicated a long-term stability of the gel formulations. The gel formulations expressed a mild acid value acceptable for topical preparations. After 6 months' storage the CHL content was highest in the gel containing non-hydrogenated lecithin liposomes, followed by the gel containing hydrogenated lecithin liposomes and liposome-free gel, indicating that the encapsulation of CHL in liposomes led to a greater stability of CHL.     

Nanostructured lipid carriers as novel ophthalmic delivery system for mangiferin: Improving in vivo ocular bioavailability

The aim of this study was to develop a novel nanostructured lipid carriers (NLCs) system to improve ocular bioavailability of mangiferin (MGN) for the potential treatment of cataract. The physicochemical properties of MGN‐loaded NLC (MGN‐NLC) formulation were characterized by particle size, polydispersity index, zeta potential, entrapment efficiency, drug loading, morphological property, and crystalline state. in vitro characteristics were investigated by drug release from NLC system, physical stability, and corneal permeation through excised rabbit cornea. Moreover, in vivo ocular tolerability was assessed by a modified Draize test and histological microscopy. Preocular retention capability was evaluated by slit‐lamp observation. Pharmacokinetic study in the aqueous humor was performed by microdialysis technique. Transmission electron microscopy depicted spherical and uniform morphology. Differential scanning calorimetry and X‐ray diffractometry displayed imperfect crystalline lattice. The optimized MGN‐NLC formulation exhibited a sustained drug release with 3 months stability and 4.31‐fold increase of in vitro corneal permeation. Furthermore, in vivo studies exhibited a high tolerance in the ocular tissues and prolonged drug retention capacity on the corneal surface. Finally, pharmacokinetic study suggested a 5.69‐fold increase of ocular bioavailability compared with MGN solution (MGN‐SOL). Therefore, NLC system is a promising approach for ocular delivery of MGN. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:3833–3844, 2012     

Influence of micronization method on the performance of a suspension triamcinolone acetonide pressurized metered-dose inhaler formulation

The purpose of this study was to investigate the influence of micronization technique on performance and stability of the model drug formulated in a suspension-based pressurized metered-dose inhaler (pMDI). The model drug, triamcinolone acetonide (TAA), was subjected to ball milling or air-jet milling prior to formulation of the pMDI. The dose delivery characteristics of the emitted aerosol cloud were monitored for the ball-milled, air-jet-milled, and unmicronized TAA pMDI formulations prior to and after storage at 25 and 40 degrees C. Cascade impaction was used to determine the aerodynamic particle size distribution of the emitted dose. Both micronization techniques reduced the drug particle size distribution and the polydispersity of the drug particles to a similar extent, but the ball-milling technique reduced the crystallinity of the drug to a greater degree compared to the air-jet-milling technique. The air-jet-milled and unmicronized TAA pMDI displayed similar aerodynamic particle size distributions of the emitted aerosol and respirable fractions over the storage period. The ball-milled TAA resulted in a pMDI formulation with the smallest aerodynamically sized particles and the highest respirable fraction compared to the air-jet-milled or unmicronized TAA pMDI formulations. The micronization techniques significantly influenced the dose delivery characteristics as a result of different initial particle size distributions, amorphous contents, and surface energies.     

Accelerated Stability Testing of a Clobetasol Propionate-Loaded Nanoemulsion as per ICH Guidelines

The physical and chemical degradation of drugs may result in altered therapeutic efficacy and even toxic effects. Therefore, the objective of this work was to study the stability of clobetasol propionate (CP) in a nanoemulsion. The nanoemulsion formulation containing CP was prepared by the spontaneous emulsification method. For the formulation of the nanoemulsion, Safsol, Tween 20, ethanol, and distilled water were used. The drug was incorporated into an oil phase in 0.05% w/v. The lipophilic nature of the drug led to the O/W nanoemulsion formulation. This was characterized by droplet size, pH, viscosity, conductivity, and refractive index. Stability studies were performed as per ICH guidelines for a period of three months. The shelf life of the nanoemulsion formulation was also determined after performing accelerated stability testing (40°C ± 2°C and 75% ± 5% RH). We also performed an intermediate stability study (30°C ± 2°C/65% RH ± 5% RH). It was found that the droplet size, conductivity, and refractive index were slightly increased, while the viscosity and pH slightly decreased at all storage conditions during the 3-month period. However, the changes in these parameters were not statistically significant (p≥0.05). The degradation (%) of the optimized nanoemulsion of CP was determined and the shelf life was found to be 2.18 years at room temperature. These studies confirmed that the physical and chemical stability of CP were enhanced in the nanoemulsion formulation.     

Physical stability, centrifugation tests, and entrapment efficiency studies of carnauba wax-decyl oleate nanoparticles used for the dispersion of inorganic sunscreens in aqueous media.

Aqueous nanoscale lipid dispersions consisting of carnauba wax-decyl oleate mixtures acting as carriers or accompanying vehicles for inorganic sunscreens such as barium sulfate, strontium carbonate, and titanium dioxide were prepared by high pressure homogenization. For the manufacture of these nanosuspensions, three pigment concentrations (%wt), namely 2, 4, and 6, and two carnauba wax-decyl oleate ratios, 1:1 and 2:1, were used, being some of these combinations chosen for stability studies. Six-month physical stability tests at 4, 20, and 40 degrees C selecting the mean particle size and the polydispersity index of the nanosuspensions as reference parameters were performed. Centrifugation tests of the nanosuspensions assessed by transmission electron microscopy and by the determination of the content of pigments and carnauba wax in the separated fractions were done. The mean particle sizes and the polydispersity indices of the nanosuspensions were not altered after six-month storages at 20 and at 40 degrees C. However, the storage of those at 4 degrees C considerably increased the particle size and polydispersity of the systems, particularly when wax-oil ratios (2:1) were used for the entrapment of the pigments. Transmission electron micrographs of centrifuged samples denoted the presence of three major fractions showing the different types of particles integrated into the nanosuspensions. Furthermore, it was observed that not all the carnauba wax participated in the entrapment of the pigment. Regarding the amount of pigment being encapsulated or bonded by the wax-oil matrices, entrapment efficiencies higher than 85.52% were reported.