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1.
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. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:2759–2769, 2009  相似文献   

2.
A new pneumatic atomizer for spray congealing, called wide pneumatic nozzle (WPN), was developed. To evaluate its performance, microparticles containing highly concentrated either solid drug (Propafenone hydrochloride, PRF) or liquid nutraceutical (Vitamin E, VE) have been prepared and characterized. The results showed that the spray congealing nozzle enabled the production of spherical and not aggregated microparticles with high yields (95% w/w) and relatively narrow size distributions; moreover, increasing the viscosity of the suspension from 50 to 500 mPa s, the particle size increased. The loading of the drug was high for microspheres (50% for PRF and 30% for VE) and the encapsulation efficiency was good for all formulations. The drug release was easily modified according to the nature of the used excipients, as both lipophilic (carnauba wax, cetearyl and stearyl alcohols) and hydrophilic (PEG 4000) carriers were employed. Moreover the results evidenced that it was possible to encapsulate actives (VE) that are in a liquid form and to enhance their availability. In conclusion the developed spray congealing nozzle was able to nebulize very viscous systems that are usually not processed by conventional apparatus and to produce microspheres with high and uniform drug content.  相似文献   

3.
The aim of this study was to encapsulate ethylhexyl methoxycinnamate (EMC), a commonly used UVB filter, in a solid lipid matrix in order to obtain microparticles and then nanoparticles to reduce its photo-instability under UV light exposure. Glyceryl behenate, rice bran wax and ozokerite were investigated for encapsulating EMC. The suspensions of nanoparticles contained 70% encapsulated EMC (relative to the lipid mass). The absorbance level at 310?nm of suspensions containing nanoparticles was more than twice that of those containing microparticles. So, decreasing the size of particles improved the efficiency of light protection, regardless of the lipid material used. Moreover, free EMC presented a 30% loss of its efficiency after 2?h of irradiation, whereas the three NLC formulations showed a loss of absorbency between 10% and 21%. The in vitro cutaneous penetration test did not show a higher potential penetration for EMC contained in nanosuspensions compared to free EMC.  相似文献   

4.
Objectives The aim was to enhance aminolevulinic acid (ALA) stability by incorporation into low‐melting microparticles prepared using a spray congealing procedure and to evaluate temperature‐triggered release, allowing topical bioavailability following melting at skin temperature. Methods ALA‐loaded Witepsol microparticles were prepared using a novel spray congealing technique. Entrapment efficiency was compared with conventional emulsion‐based methods and modelled drug release profiles determined using a membrane separation technique. Raised receiver medium temperature was used to determine triggered release. Bioavailability and lipid‐mediated enhancement of ALA penetration were determined in excised murine skin. Key findings ALA‐loaded Witepsol microparticles were spherical, with a mean diameter of 20 μm. Loading and stability studies demonstrated effective encapsulation, ranging from 91% to 100%, with no evidence of degradation to pyrazine derivatives. ALA release correlated with dissolution medium temperature, triggered at temperatures close to that of skin. Results suggested that molten Witepsol enhanced cutaneous permeation, whereas incorporation of microparticles in a semi‐solid vehicle attenuated ALA penetration. Optimal use was direct application under occlusion. Conclusions Spray congealing is superior to the emulsion‐based procedures with respect to encapsulation efficiency of ALA in Witepsol matrices, providing temperature‐triggered release, enhanced stability and improved penetration of ALA through keratinised skin. These features could improve ALA delivery to superficial lesions as part of photodynamic therapy.  相似文献   

5.
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.  相似文献   

6.
The purpose of this research was to prepare a sustained release drug delivery system of venlafaxine hydrochloride by using a wax matrix system. The effects of bees wax and carnauba wax on drug release profile was investigated. A 32 full factorial design was applied to systemically optimize the drug release profile. Amounts of carnauba wax (X1) and bees wax (X2) were selected as independent variables and release after 12 h and time required for 50% (t50) drug release were selected as dependent variables. A mathematical model was generated for each response parameter. Both waxes retarded release after 12 h and increases the t50 but bees wax showed significant influence. The drug release pattern for all the formulation combinations was found to be approaching Peppas kinetic model. Suitable combination of two waxes provided fairly good regulated release profile. The response surfaces and contour plots for each response parameter are presented for further interpretation of the results. The optimum formulations were chosen and their predicted results found to be in close agreement with experimental findings.  相似文献   

7.
Lipid microparticles loaded with the complex between hydroxypropyl-β-cyclodextrin (HP-β-CD) and the sunscreen agent, butyl methoxydibenzoylmethane (BMDBM) were evaluated for their effect on the UV filter percutaneous penetration. The microparticles were prepared by the melt emulsification technique using tristearin as lipidic material and hydrogenate phosphatidylcholine as the surfactant. Human skin penetration was investigated in vivo by the tape stripping technique, a minimal invasive procedure based on the progressive removal of the upper cutaneous layers (stratum corneum) with adhesive tape strips. The amount of sunscreen fixed to each strip was determined by HPLC after solvent extraction. The recovery of the UV filter from spiked adhesive tapes was >94.4% and the precision of the method was better than 7.6% relative standard deviation. Non-encapsulated BMDBM, its complex with HP-β-CD, the lipid microparticles loaded with the sunscreen alone or the BMDBM/HP-β-CD complex were introduced into oil-in-water emulsions and applied to human volunteers. Compared to the cream with the non-encapsulated sunscreen agent (percentage of the applied dose penetrated, 9.7%±2.5), the amount of BMDBM diffusing into the stratum corneum was increased by the formulations containing the BMDBM/HP-β-CD complex (17.1%±3.2 of the applied dose) or the microparticles loaded with BMDBM only (15.1%±2.7 of the applied dose). On the contrary, a significant decrease in the level of UV filter penetrated into the stratum corneum was achieved by the cream containing the microencapsulated BMDBM/HP-β-CD complex (percentage of the applied dose penetrated, 6.0%±1.5). The reduced BMDBM percutaneous penetration attained by the latter system should enhance the UV filter efficacy and limit potential toxicological risks.  相似文献   

8.
The aim of this study was to encapsulate ethylhexyl methoxycinnamate (EMC), a commonly used UVB filter, in a solid lipid matrix in order to obtain microparticles and then nanoparticles to reduce its photo-instability under UV light exposure. Glyceryl behenate, rice bran wax and ozokerite were investigated for encapsulating EMC. The suspensions of nanoparticles contained 70% encapsulated EMC (relative to the lipid mass). The absorbance level at 310?nm of suspensions containing nanoparticles was more than twice that of those containing microparticles. So, decreasing the size of particles improved the efficiency of light protection, regardless of the lipid material used. Moreover, free EMC presented a 30% loss of its efficiency after 2?h of irradiation, whereas the three NLC formulations showed a loss of absorbency between 10% and 21%. The in?vitro cutaneous penetration test did not show a higher potential penetration for EMC contained in nanosuspensions compared to free EMC.  相似文献   

9.
The objective of the present study was to determine the effects of hydroxypropyl-beta-cyclodextrin (HPCD) complexation on the transdermal penetration and photostability of a model ultraviolet A (UVA) absorber, butyl methoxydibenzoylmethane (avobenzone), and to determine the influence of complexation on in vivo photoprotection. Avobenzone-HPCD complexation was demonstrated by differential scanning calorimetry. Formulations containing 0.12 mg/ml avobenzone and up to 30% (w/w) HPCD were prepared. Transdermal penetration was conducted using a modified Franz diffusion cell apparatus. As the concentration of HPCD was increased from 0% to 20%, transdermal permeation increased. Maximum flux occurred at 20% HPCD, where sufficient cyclodextrin was present to completely solubilize all avobenzone. When the concentration of HPCD was increased to 30%, transdermal penetration decreased, suggesting the formation of an avobenzone reservoir on the skin surface. Photostability of avobenzone was investigated under 100, 250, and 500 kJ/m2 UVA irradiation. The 30% HPCD formulation was the most photostable, followed by 20%, 10%, and 0% formulations. In vivo, the 30% HPCD formulation afforded the best photoprotection, as evidenced by the lowest extent of sunburn cell formation and edema induction. This work indicates that inclusion of HPCD in sunscreen formulations may enhance photoprotection by reducing both skin penetration and photodecomposition of UV absorbers.  相似文献   

10.
Introduction: In any manufacturing process, the success of producing an end product with the desired properties and yield depends on a range of factors that include the equipment, process and formulation variables. It is the interest of manufacturers and researchers to understand each manufacturing process better and ascertain the effects of various manufacturing-associated factors on the properties of the end product. Unless the manufacturing process is well understood, it would be difficult to set realistic limits for the process variables and raw material specifications to ensure consistently high-quality and reproducible end products. Over the years, spray congealing has been used to produce particulates by the food and pharmaceutical industries. The latter have used this technology to develop specialized drug delivery systems.

Areas covered: In this review, basic principles as well as advantages and disadvantages of the spray congealing process will be covered. Recent developments in spray congealing equipment, process variables and formulation variables such as the matrix material, encapsulated material and additives will also be discussed.

Expert opinion: Innovative equipment designs and formulations for spray congealing have emerged. Judicious choice of atomizers, polymers and additives is the key to achieve the desired properties of the microparticles for drug delivery.  相似文献   

11.
This work is aimed to evaluate the application of photoacoustic spectroscopy (PAS) in the characterization of inclusion complexes of benzophenone-3 (BZ-3) and hydroxypropyl-β-cyclodextrin (HPCD) and to analyze the ex vivo percutaneous penetration of sunscreens and their reaction with the skin. The formation of inclusion complexes of BZ-3 and HPCD was performed by co-precipitation in stoichiometric ratios of 1:1 and 1:2. Thermal analysis and PAS characterized these inclusion complexes, and they indicated that the stoichiometric ratio of 1:2 was best. Sunscreen formulations were prepared and applied on the ears of rabbits. PAS suggested that the formulation with the complex resulted in lower penetration of BZ-3. Histological analysis demonstrated that the use of the formulation with BZ-3 was associated with an increase in the comedogenic effect and the presence of acanthosis, while no such effect was found in the formulation with the complex. The formulation with the BZ-3-HPCD complex is a promising strategy for improving the photoprotective effect of BZ-3. PAS can be used in the study of inclusion complexes with cyclodextrins and the evaluation of the percutaneous penetration of sunscreen formulations. Further tests are being conducted using PAS to monitor in vivo changes in the optical absorption spectra of formulations and to investigate their photostability.  相似文献   

12.
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.  相似文献   

13.
Agricultural workers are encouraged to use sunscreen to decrease the risk of UV-related skin cancer. Our previous studies have shown certain commercial sunscreens to be penetration enhancers. The focus of this project is to determine whether active ingredients in sunscreen formulations (i.e., the UV absorbing components and insect repellants for the sunscreen/bug repellant combinations) also act as dermal penetration enhancers for herbicides in vitro. The total percentages of 2,4-dichlorophenoxyacetic acid (2,4-D) penetrating through hairless mouse skin in 24 h ranged from 54.9 +/- 4.7 for the no sunscreen control to 86.9 +/- 2.5 for padimate-o. Of the active ingredients tested (7.5% octyl methoxycinnamate, 7% octocrylene, 0.6% oxybenzone, 5% homosalate, 5% octyl salicylate, 8% padimate-o, 10% sulisobenzone, and 9.5% and 19% N,N-diethyl-m-toluamide [DEET]), all but octocrylene led to a significant increase in total 2,4-D penetration as compared to the control (P < 0.05), and only octocrylene and oxybenzone did not significantly decrease the corresponding lag time. Octyl salicylate (P < 0.01) and octyl methoxycinnimate (P < 0.05) significantly increased the 3H2O penetration across mouse skin, indicating physical damage to the stratum corneum. Additional studies demonstrated that the penetration enhancement seen across hairless mouse skin also occurred with human skin. Thus, the active ingredients of sunscreen formulations enhance dermal penetration of the moderately lipophilic herbicide 2,4-D.  相似文献   

14.
AIMS: Topical sunscreens are routinely applied to the skin by a large percentage of the population. This study assessed the extent of absorption of a number of common chemical sunscreen agents into and through human skin following application of commercially available products. METHODS: Sunscreen products were applied to excised human epidermis in Franz diffusion cells with the amount penetrating into and across the epidermis assessed by h.p.l.c. for 8 h following application. RESULTS: All sunscreen agents investigated penetrated into the skin (0.25 g m-2 or 14% of applied dose), but only benzophenone-3 passed through the skin in significant amounts (0.08 g m-2 or 10% of the applied dose). With one exception, suncreen agents in corresponding products marketed for adults and children had similar skin penetration profiles. CONCLUSIONS: Whilst limited absorption across the skin was observed for the majority of the sunscreens tested, benzophenone-3 demonstrated sufficiently high penetration to warrant further investigation of its continued application.  相似文献   

15.
Context: Salbutamol sulphate is widely used as bronchodilator for the treatment of asthma. Its use is limited by the relatively short duration of action and hence sustained delivery of salbutamol sulphate offers potential benefits to patients.

Objective: This study explores the preparation of lipid microparticles (LMs) as biocompatible carrier for the prolonged release of salbutamol sulphate.

Materials and methods: The LMs were produced using different lipidic materials and surfactants, by classical melt emulsification-based methods (oil-in-water and water-in-oil-in-water emulsions) and the spray congealing technique.

Results: For the LMs obtained by melt emulsification a lack of release modulation was observed. On the other hand, the sustained release of salbutamol sulphate was achieved with glyceryl behenate microparticles prepared by spray congealing. These LMs were characterized by scanning electron microscopy, X-ray diffractometry and differential scanning calorimetry. The drug loading was 4.72% (w/w). The particle size distribution measured by laser diffraction and electrical zone sensing was represented by a volume median diameter (Dv50) of 51.7–71.4 µm. Increasing the atomization air pressure from 4 to 8 bar produced a decrease of the Dv50 to 12.7–17.5 µm.

Conclusions: Incorporation of the hydrophilic salbutamol sulphate into LMs with sustained release characteristics was achieved by spray congealing.  相似文献   

16.
Organic sunscreens may decrease their protective capability and also behave as photo-oxidants upon ultraviolet radiation (UVR) exposure. The present study investigated the effect of a cream gel formulation containing the UV filters benzophenone-3, octyl methoxycinnamate, and octyl salicylate on skin superoxide dismutase (SOD) after a single dose of UVR (2.87 J/cm2). The retention of these UV filters was first evaluated in vivo using hairless mice to guarantee the presence of the filters in the skin layers at the moment of irradiation. The in vivo effect of the UV filters on skin SOD was then assayed spectrophotometrically via the reduction of cytochrome c. The cream gel formulation promoted the penetration of the three UV filters into the epidermis and the dermis at one hour post-application. A significant decrease in SOD activity was observed in irradiated animals treated with sunscreen formulation. However, no effect on SOD activity in skin was observed by the isolated presence of the sunscreens, the formulation components, or the exposure to UVR. The sunscreens may have formed degradation products under UVR that may have either inhibited the enzyme or generated reactive species in the skin.  相似文献   

17.
Drug-free microparticles were prepared using a spray congealing process with the intention of studying the influence of processing parameters. By varying the atomizing pressure and liquid feed rate, microparticles with median sizes (d(0.5)) from 58 to 278 μm were produced, with total process yields ranging from 81% to 96%. An increased liquid feed rate was found to increase microparticle size, and higher atomizing pressures were found to decrease microparticle size. Greater change in microparticle size was achieved by varying atomizing pressure, which can be considered a dominant process parameter regarding microparticle size. In addition, microparticles with glimepiride, a model poorly water-soluble drug, were prepared by spray congealing using three different hydrophilic meltable carriers: Gelucire® 50/13, poloxamer 188, and PEG 6000. Spherical microparticles with relatively smooth surfaces were obtained, with no drug crystals evident on the surfaces of drug-loaded microparticles. XRPD showed no change in crystallinity of the drug due to the technological process of microparticle production. All glimepiride-loaded microparticles showed enhanced solubility compared to pure drug; however, Gelucire® 50/13 as a carrier represents the most promising approach to the dissolution rate enhancement of glimepiride. The influence of storage (30 °C/65% RH for 30 days) on the morphology of glimepiride/Gelucire® 50/13 microparticles was studied, and the formation of leaf-like structures was observed (a “blooming” effect).  相似文献   

18.
Gupta  Vinod K.  Zatz  Joel L.  Rerek  Mark 《Pharmaceutical research》1999,16(10):1602-1607
Purpose. The objectives of this study were to develop an in vitro model for studying sunscreen permeation in skin, and evaluate the influence of formulation differences. Methods. The sunscreens studied were two of the most widely used agents, octyl methoxycinnamate (OMC) and benzophenone-3. Preparations containing radiolabeled actives were applied to micro-Yucatan pig skin dermatomed to a thickness of 250–300 m as a finite dose in a flow-through diffusion system. At the end of each experiment the amounts removed by washing, retained inside stratum corneum (SC) and penetrated into receptor and viable skin were determined. Results. The two sunscreens reached a peak level in SC within an hour. Benzophenone-3 penetrated skin to a greater extent than OMC. The opposite was true when comparisons of SC retention were made. The ratio of retained to penetrated amount of sunscreens from a hydroalcoholic formulation at the end of 10 hours was higher when the sunscreens were present together than alone. Conclusions. Despite the highly lipophilic nature of sunscreens, particularly OMC, SC is the rate limiting skin layer for penetration. Penetration and SC retention were formulation dependent. The ratio of SC content to the amount penetrated is a useful tool for evaluating sunscreen permeation.  相似文献   

19.
The purpose of this study was to evaluate the in vitro transdermal permeation and skin accumulation of one ultraviolet (UV) absorber-octyl methoxycinnamate (OMC)-through pig skin and to determine the quantity of OMC in the skin surface and different pig skin layers (stratum corneum, viable epidermis, dermis, and receptor fluid). Four cases have been considered: the application of oil-in-water (O/W) and water-in-oil (W/O) emulsions containing the same filter free and encapsulated in nanocapsules (NC). The influence of the carrier on the percutaneous penetration was studied. Data showed that UV absorber exhibited increases in skin accumulation when is formulated in emulsions in free form. Skin accumulation of OMC-free in the emulsions was significantly (P < 0.05) greater than that of OMC-encapsulated for all formulations investigated. OMC-free skin accumulation ranged from 127.8 +/- 22.8 microg/cm(2) (O/W emulsion) to 172.1 +/- 12.9 microg/cm(2) (W/O emulsion). OMC-encapsulated skin accumulation ranged from 50.3 +/- 13.1 microg/cm(2) to 43.0 +/- 6.5 microg/cm(2) at NC-O/W and NC-W/O, respectively. No significant differences were found in the transdermal permeation of cinnamate for any of the formulations tested. The results of this study demonstrate that the inclusion of OMC-encapsulated in sunscreen formulations decreases the skin accumulation of the cinnamate since the in vitro release mechanism of OMC-nanocapsules is governed by hydrophobicity and crystallinity of the polymer and by the high lipophilicity of the drug. The crystallinity of the polymer have the ability of reflecting and scattering UV radiation on their own thus leading to photoprotection without the need for molecular sunscreens.  相似文献   

20.
The aim of this study was the in vitro evaluation of the efficacy of two different carrier systems for the molecular sunscreen benzophenone-3. One carrier system was a conventional o/w emulsion, the other consisted of highly crystalline lipid nanoparticles (CLN). It was observed that CLN act as physical sunscreens themselves and show improved photoprotection compared with a placebo emulsion with the same lipid content. Incorporation of a molecular sunscreen further improves the protection level in a synergistic way. This in vitro study based on the Transpore test by Diffey showed that the amount of molecular sunscreen can be decreased by up to 50% while maintaining the UV protection efficacy. Therefore, the use of CLN as an active carrier for sunscreens is a promising innovation.  相似文献   

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