Solid lipid microparticles for the stability enhancement of a dopamine prodrug.

The oral or peripheral administration of dopamine for the treatment of Parkinson's disease is hampered by its extensive metabolism and inability to cross the blood-brain barrier. Consequently, the enhancement of dopamine stability in physiologic environments and its brain targeting appear useful in formulation development. We propose the preparation and characterization of solid lipid microparticles based on tristearin as a sustained delivery system for dopamine. The microparticles were produced by conventional hot emulsion techniques. The synthesis of a new valeroyl ester of dopamine (3,4-O-divaleroyl-dopamine, DVD) was necessary to obtain its encapsulation in the microparticles. DVD appeared totally hydrolyzed to dopamine in human plasma within 40 s. The amount of encapsulated DVD in microparticles was 2.67 ± 1.2%. The mean diameter of particles was 14.2 ± 4.8 µm. The DVD release from microparticles was characterized by an initial burst of 20% of incorporated prodrug and a continuous slow release thereafter. The microparticles were able to stabilize DVD in its solid form. In human plasma, DVD encapsulated in microparticles hydrolyzed with a markedly reduced rate in comparison with free prodrug: after 15 min, 35.8% of DVD was still detectable. The DVD-loaded microparticles could represent a potential system for dopamine uptake in the brain, following nasal administration.

Photostabilization effect of quercetin on the UV filter combination, butyl methoxydibenzoylmethane-octyl methoxycinnamate.

The aim of the study was to investigate the effect of the natural antioxidant quercetin on the photostability of the most widely used combination of UVA (320-400 nm) and UVB (290-320 nm) filters, respectively butyl methoxydibenzoylmethane (BMDBM) and octyl methoxycinnamate (OMC). In order to reproduce the conditions prevalent in commercial sunscreen products, the stabilizing efficacy of quercetin was evaluated in model creams containing BMDBM (3%, wt/wt) together with OMC (4%, wt/wt) and exposed to a solar simulator at an irradiance corresponding to natural sunlight. Quercetin was found to enhance the photostability of the two UV filters in a concentration-dependent way. Addition of quercetin to the sunscreen formulation significantly reduced the photodegradation of BMDBM and OMC from 40.3 +/- 2.4 to 27.7 +/- 2.6% and from 51.3 +/- 2.1 to 42.2 +/- 2.0%, respectively. Moreover, comparative photodegradation studies demonstrated that quercetin was much more effective and at a lower concentration than commonly used stabilizer (octocrylene) and antioxidants (vitamin E, butylated hydroxyanisole). In vitro determination of the UVB and UVA protection parameters showed that the quercetin-based formulation fulfilled the official requirements on sunscreen products. Because of its photostabilizing and multiple antioxidant properties, quercetin represents a useful additive for the formulation of effective broad-spectrum sunscreens containing BMDBM and OMC.

Solid lipid budesonide microparticles for controlled release inhalation therapy.

A solid lipid microparticle system containing budesonide was prepared by oil in water emulsification followed by spray drying. The solid lipid system was studied in terms of morphology, particle size distribution, crystallinity, thermal properties, aerosol performance, and dissolution/diffusion release. The microparticle system was also compared to conventional spray-dried crystalline and amorphous budesonide samples. The particle size distributions of the crystalline, amorphous, and solid lipid microparticles, measured by laser diffraction, were similar; however, the microparticle morphology was more irregular than the spray-dried drug samples. The thermal response of the solid lipid microparticles suggested polymorphic transition and melting of the lipid, glycerol behenate (at approximately 48 degrees C and approximately 72 degrees C). No budesonide melting or crystallisation peaks were observed, suggesting that the budesonide was integrated into the matrix. X-ray powder diffraction patterns of the crystalline and amorphous budesonide were consistent with previous studies while the solid lipid microparticles showed two peaks, at approximately 21.3 and 23.5 2theta suggesting the metastable sub-alpha and primarily beta' form. Analysis of the in vitro diffusion/dissolution of the formulations was studied using a flow through model and curves analysed using difference/similarity factors and fitted using the Higuchi model. Regression analysis of this data set indicated differences in the t (0.5), where values of 49.7, 35.3, and 136.9 min were observed for crystalline, amorphous, and the solid lipid microparticles, respectively. The aerosol performance (<5 microm), measured by multistage liquid impinger, was 29.5%, 27.3%, and 21.1 +/- 0.6% for the crystalline, amorphous, and the solid lipid microparticles, respectively. This study has shown that solid lipid microparticles may provide a useful approach to controlled release respiratory therapy.

Incorporation in lipid microparticles of the UVA filter, butyl methoxydibenzoylmethane combined with the UVB filter, octocrylene: effect on photostability.

The aim of this study was to reduce the photoinstability of butyl methoxydibenzoylmethane (BMDBM), the most widely used UVA filter, by incorporating it in lipid microparticles (LMs) alone or together with the UVB filter octocrylene (OCR), acting also as photostabilizer. Microparticles loaded with BMDBM or with combined BMDBM and OCR were produced by the hot emulsion technique, using glyceryl behenate as lipid material and poloxamer 188 as surfactant. The LMs were characterized by release studies, scanning electron microscopy, and powder X-ray diffractometry. The BMDBM and OCR loading was 15.2% and 10.6%, respectively. In order to reproduce the conditions prevalent in commercial sunscreen products, the photoprotective efficacy of the LMs was evaluated after their introduction in a model cream (oil-in-water emulsion) containing a mixture of UVA and UVB filters. A small but statistically significant decrease in BMDBM photodegradation was obtained when the UVA filter was encapsulated alone into the LMs (the extent of degradation was 28.6% +/-2.4 for non-encapsulated BMDBM and 26.0% +/-2.5 for BMDBM-loaded microparticles). On the other hand, the co-loading of OCR in the LMs produced a more marked reduction in the light-induced decomposition of microencapsulated BMDBM (the UVA filter loss was 21.5% +/-2.2). Therefore, incorporation in lipid microparticles of BMDBM together with the sunscreen OCR is more effective in enhancing the UVA filter photostability than LMs loaded with BMDBM alone.

Co-loading of a photostabilizer with the sunscreen agent, butyl methoxydibenzoylmethane in solid lipid microparticles.

The sunscreen agent, butyl methoxydibenzoylmethane (BMDBM), one of the most widely used UV-A filter, undergoes decomposition under sunlight exposure, which is a limiting factor on its overall performance. To reduce the sunscreen photodegradation, this study investigates the incorporation into solid lipid microparticles (SLMs) of BMDBM together with the photostabilizer, 4-methylbenzylidene camphor (MBC). The microparticles were produced by the melt dispersion technique using various lipid materials (tristearin, glyceryl behenate, and stearic acid) and hydrogenated phosphatidylcholine as the surfactant. The highest retention capacity for BMDBM and MBC was achieved with tristearin microparticles. These SLMs were characterized by scanning electron microscopy and powder X-ray diffraction analyses. The BMDBM and MBC loading was 10.4 and 10.1%, respectively. The efficacy of the SLMs was evaluated after their introduction in a conventional cream (oil-in-water emulsion). The light-induced decomposition of BMDBM was decreased by encapsulation into the SLMs (the extent of degradation was 33.8 +/- 5.5% for unencapsulated BMDBM/MBC and 25.3 +/- 4.2% for BMDBM-loaded microparticles in conjunction with free MBC). Moreover, the co-loading of the MBC stabilizer in the SLMs produced a further reduction of the photodegradation of the UV-A filter (the BMDBM loss was 16.9 +/- 5.9%) compared with the microparticles containing BMDBM without MBC. Therefore, incorporation in lipid microparticles of BMDBM together with the MBC photostabilizer is more effective in enhancing the UV-A filter photostability than the SLMs loaded with BMDBM alone.

Incorporation of quercetin in lipid microparticles: effect on photo- and chemical-stability.

Lipid microparticles loaded with the flavonoid, quercetin were developed in order to enhance its stability in topical formulations. The microparticles were produced using tristearin as the lipid material and phosphatidylcholine as the emulsifier. The obtained lipoparticles were characterized by release studies, scanning electron microscopy and powder X-ray diffractometry. The quercetin loading was 12.1% (w/w). Free or microencapsulated quercetin was introduced in a model cream formulation (oil-in-water emulsion) and irradiated with a solar simulator. The extent of photodegradation was measured by high-performance liquid chromatography. The light-induced decomposition of quercetin in the cream vehicle was markedly decreased by incorporation into the lipid microparticles (the extent of degradation was 23.1+/-3.6% for non-encapsulated quercetin compared to 11.9+/-2.5% for the quercetin-loaded microparticles) and this photostabilization effect was maintained over time. Moreover, the chemical instability of quercetin, during 3-month storage of the formulations at room temperature and in the dark, was almost completely suppressed by the lipid microparticle system. Therefore incorporation of quercetin in lipoparticles represents an effective strategy to enhance its stability in dermatological products.

Evaluation of spray congealing as technique for the preparation of highly loaded solid lipid microparticles containing the sunscreen agent, avobenzone.

Solid lipid microparticles (SLMs) loaded with high amounts of the sunscreen agent, butyl methoxydibenzoylmethane (avobenzone) were prepared in order to reduce its photoinstability. The microparticles were produced, using carnauba wax as lipidic material and phosphatidylcholine as the surfactant, by the classical melt dispersion method or the spray congealing technique with pneumatic atomizer. The sunscreen agent loading was 40.1-48.5% (w/w), with no significant differences between the production methods. However, release studies indicated that spray congealing enabled a more efficient modulation of avobenzone release from the SLMs (26% of encapsulated avobenzone released after 2 h as compared to 60% for melt dispersion). The photoprotective efficacy of the SLMs was evaluated after their introduction in a model cream. A statistically significant decrease of the light-induced degradation of avobenzone was obtained by the SLMs prepared by the melt dispersion procedure (the extent of degradation was 38.6 +/- 3.6% for nonencapsulated avobenzone and 32.1 +/- 4.3% for the microparticle-entrapped sunscreen). On the other hand, the SLMs produced by spray congealing achieved a more marked reduction in avobenzone photodecomposition to 15.4 +/- 4.1%. Therefore, the spray congealing technique was superior to the classical melt dispersion method for rapid and solvent free production of SLMs with a high avobenzone loading capacity.

Influence of solid lipid microparticle carriers on skin penetration of the sunscreen agent, 4-methylbenzylidene camphor.

The objective of this study was to prepare lipid microparticles (LMs) loaded with the sunscreen agent, 4-methylbenzylidene camphor (4-MBC), to achieve decreased skin penetration of this UV filter. The microparticles were produced by the melt dispersion technique using tristearin as lipidic material and hydrogenated phosphatidylcholine as the surfactant. The obtained microparticles were characterized by scanning electron microscopy and differential scanning calorimetry. Release of 4-MBC from the LMs was found to be slower than its dissolution rate. The influence of the LMs' carrier system on percutaneous penetration was evaluated after their introduction in a model topical formulation (emulsion). In-vitro measurements were performed with cellulose acetate membranes in Franz diffusion cells. The 4-MBC release and diffusion was decreased by 66.7-77.3% with the LM formulation, indicating that the retention capacity of the microparticles was maintained after incorporation into the emulsion. In-vivo human skin penetration of 4-MBC was investigated by tape stripping, a technique for selectively removing the upper cutaneous layers. The amount of sunscreen penetrating into the stratum corneum was greater for the emulsion containing non-encapsulated 4-MBC (36.55% of the applied dose) compared with the formulation with the sunscreen-loaded microparticles (24.57% of the applied dose). The differences between the two formulations were statistically significant in the first (2-4) horny layer strips. Moreover, the LMs' effect measured in-vivo was less pronounced than in-vitro. The increased 4-MBC retention on the skin surface achieved by its incorporation in the LMs should enhance its efficacy and reduce the potential toxicological risk associated with skin penetration.