ABSTRACT
Objective: To reduce or avoid the volatilization loss of camphor (CA) in the industrialized preparation of cataplasm, using the inclusion technology of HP-β-CD. Methods: The HP-β-CD inclusion compound of CA (CA-HP-β-CD) was prepared by the constant temperature stirring method. The preparation processing of CA-HP-β-CD was optimized with inclusion efficiency as an index, and the pharmaceutical properties of CA-HP-β-CD were characterized by DSC, UV and SEM. The CA and CA-HP-β-CD were prepared to cataplasm at the industrial-scale production respectively, then the content of CA was determined and the statistical analysis was carried out. Results: The inclusion efficiency of CA-HP-β-CD for CA was (68.57 ± 1.26)% when the CA-HP-β-CD was prepared with the mass ratio of CA to HP-β-CD 1:3, the working temperature at 35 ℃ and stirring at 300 r/min for 4.0 h. The DSC, UV and SEM scans showed that there was a good compatibility between CA and HP-β-CD, and CA could be fully encapsulated by HP-β-CD and formed a stable inclusion complex of CA-HP-β-CD. Results of industrial-scale production of cataplasm for CA and CA-HP-β-CD revealed that the retention rate (actual content/feeding quantity) were (80.13 ± 1.05)% and (39.45 ± 1.38)%, respectively. And there was a statistically significant difference between them (t-test, P < 0.01), indicating that the HP-β-CD inclusion complex effectively reduce the volatilization loss of camphor CA. Conclusion: The volatilization loss of CA at the industrial-scale production of cataplasm was effectively reduced by the CA-HP-β-CD, which improves the utilization rate of CA and reduces the cost, and provides ideas and reference for the research and development of cataplasm of volatile drugs.
ABSTRACT
Microspheres (MS) are an excellent transarterial chemoembolization carrier for cancer treatment. Then the Bletilla striata polysaccharide (BSP) that was isolated from the rattan of Bletilla striata was used as skeleton material, and the matrine (ME) loaded Bletilla striata polysaccharide microspheres (ME-BSPMS) were prepared by emulsify-chemical crosslinking method. ME-BSPMS was characterized for appearance shape, particle size, drug loading, swelling ratio, suspension property, drug entrapment condition and in vitro release characteristics. The results showed that the ME-BSPMS appeared as round spherical and smooth shape by SEM, with an average size of (85 ±7) μm. ME-BSPMS with a good suspension in physiological saline and the swelling ratio could reach upwards of (53 ±4.2)% in 20 minutes, also with a large amount of drug loading of (30.12 ±3.25)%. The results of DSC scanning indicate that good compatibility exists between the ME and BSP, and the ME could be embedded fully in the matrix of the ME-BSPMS. The accumulation drug release from ME-BSPMS was (25.38 ±1.57)% at 12 h, this suggests that the ME-BSPMS has a good sustained release effect. These results indicate that the ME-BSPMS may be a promising transarterial chemoembolization carrier for cancer treatment.
ABSTRACT
Flexible liposomes are an excellent drug delivery nanocarrier, however, the leakage of drugs from liposomes has become common technical obstacle in the industry and also hindered its further application seriously. It is very urgent and necessary to avoid or reduce the leakage of drugs from liposomes. In this work, five kinds of essential oils such as Folium Artemisiae Argyi oil (FA), Folium Eucalypti oil (FE), Arabian Jasmine oil (AJ), Syzygium Aromaticum oil (SA) and Fructus Forsythiae oil (FF) were encapsulated in the lipid bilayer of palmatine chloride (PC) loaded flexible nano-liposomes (PFL), then the optimal essential oil and its dosage level were determined by the external leakage curve of PC. The female Japanese white rabbits were used to evaluate the vaginal irritancy potential of liposomes samples. The pharmaceutical properties such as encapsulation efficiency, particle size, zeta potential, deformability and structure of liposomes samples were evaluated. In order to investigate the permeability of liposomes samples to deliver PC across skin and mucous membrane in vitro, the side-by-side diffusion cells were used. The results showed that the leakage of hydrosoluble PC from PFL was reduced at different degrees by the essential oils in the lipid bilayer of PFL, however, the reduction in leakage degree was obviously higher for FA than thoses of FE, AJ, SA and FF (P < 0.05), and the highest reduction in leakage degree was obtained when the FA and lipid mass ratio was 1:6. The encapsulation efficiency, particle size, zeta potential and deformability of PFL were not significantly changed after FA was encapsulated in the lipid bilayer of the PFL (P > 0.05), so did the lamellar structure of PFL. In addition, the transdermal and transmucosal permeability of PC were also enhanced obviously by encapsulating FA in the lipid bilayer of PFL, and there was no vaginal/vulvar irritation observed in the rabbits. In summary, the drug leakage was reduced by encapsulating suitable essential oil (such as FA) in the lipid bilayer of flexible liposomes, and the vaginal mucosa permeability were improved for the drug. These results provide a novel technique in the improvement of flexible nano-liposomes for drug delivery.
ABSTRACT
OBJECTIVE: To prepare palmatine-loaded flexible nano-liposomes (PFNL) and study their pharmaceutical properties, in order to lay the foundation for the industral application. METHODS: The flexible nano-liposomes were prepared by thin-film homogenization method with propyleneglycol (PG) as softening agent. The entrapment rate of palmatine was evaluated by protamine aggregation method and HPLC. The effects of concentrations of phosphatidylcholine (PSC), cholesterol (CH), and PG on the entrapment efficiency of palmatine were also investigated. The pharmaceutical properties of PFNL were evaluated by TEM, PCS and CLSM. The deformation of PFNL was determined by its relative rate of permeating the microporous filter membrane. The coagulation rate constant (K) was measured by constant temperature conductivity method. The side-by-side diffusion cells and pig vaginal mucosa were used to investigate the characteristics of the release of palmatine from PFNL in vitro, and the effects of PFNL on the expression of cytokines (SLPI, LF and SP-D) were investigated and compared with classic liposomes and lotion of palmatine. RESULTS: The palmatine entrapment efficiency was (78 ±2.13)% when the PFNL were prepared with PSC (3%), CH (0.02%), and PG (20%). The prepared nano flexible liposomes had a closed spherical or elliptical shape and appeared as multi-lamellar vesicles under the TEM and CLSM. The calculated mean size was (185 ±19) nm, and the Zeta potential was (-53 ±2.27) mV. The deformation of PFNL was (79 ± 5.75)%. The coagulation rate constant (K) of PFNL was always lower than that of traditional palmatine- loaded liposomes. The accumulated permeation amount of palmatine from the PFNL at 6.0 h was 1.53 and 2.86 folds of those of classic liposomes and lotion, respectively. Moreover, the expressions of cytokines (SLPI, LF and SP-D) in female SD rats after being treated with PFNL, PCL and PL were similar to that of the control group. CONCLUSION: The prepared PFNL have high encapsulation efficiency, good stability and safety, and greatly increase the vaginal mucosa permeability of palmatine. Flexible nano-liposomes may be a useful drug delivery carrier for the gynecological application of palmatine.
ABSTRACT
Objective: Through the studies on pilot production of the cataplasma of Chinese materia medica (CMM) containing volatile oil, to provide a rational and feasible preparation technology for the pilot production of CMM cataplasma, so as to promote the development of CMM cataplasma. Methods: The CMM containing volatile oil was extracted by steam distillation method (SDM), ethanol reflux extraction (ERE), and CO2 supercritical fluid extraction (SFE), respectively. The extracts were prepared to cataplasma in order to investigate the effects of extracting methods on the preparation process and quality of CMM cataplasma. The effects of micellar solubilization in the distilled liquid of STM on the quality of cataplasma such as adhesiveness, flexibleness, and stability were also investigated. Results: There was the significant difference among the groups of STM, ERE, and SFE on the quality of cataplasma. The extract by STM was beneficial to the preparation process and enhancement of the quality of cataplasma obviously, while the distilled liquid by STM would cause some limitations such as oil-water separation and volatile oil volatilization losses, which could contribute to obvious difference among batches. These disadvantages by STM would be overcome by the adoption of micellar solubilization technology and the stability would be increased (P < 0.01); segregation happened for the extract by ERE at room temperature, thereby, the water bath heating was needed in the preparation; this characteristics would cause the homogeneous appearance of cataplasma due to some black spots, lower flexibleness of matrix, and the preparation was not easy to control; the extract by SFE contained a lot of impurity of grease and performed half solid. As a result, it was very difficult to blend the extract by SFE with other materials uniformly, the adhesive force of cataplasma was also reduced. In addition, the cost of higher energy consumption and production was another disadvantage for SFE. Conclusion: The STM followed by micellar solubilization would be a feasible preparation technology for the pilot production of CMM cataplasma containing volatile oil, so it is worth popularizing and applying widely.
ABSTRACT
Objective: To study the characteristics and mechanism of transdermal delivery of sinomenine hydrochloride (SH) through mouse skin treated by solid silicon microneedle arrays. Methods: The amount of SH was determined by HPLC system. Hairless rat skin was pretreated with microneedle arrays. The side-by-side diffusion cell method was used to investigate the effects of needlepoint shape, different insertion forces, retention time, and number of microneedles on transdermal SH delivery. Skin samples treated by microneedles were made into paraffin sections for histological examination and were viewed by brightfield microscopy. Results: The skin pretreated with microneedle arrays had a remarkable enhancement of SH transport compared with passive diffusion group (P<0.01); the flat tipped microneedles were more effective than the sharp tipped microneedles in enhancing the skin permeability. The accumulation of SH increased with the enhancement of insertion force; however, when the insertion force exceeded 5.0 N, the accumulation of SH no longer increased. The skin permeability was enhanced with the increase of retention time; when the retention time exceeded 1.0 min, it no longer increased SH accumulation. Although skin permeability increased with the microneedle number, there was no linear correlation was found. Histological examination showed that microneedle piercing created micro-conduits in skin. Conclusion: Microneedles can create conduits in rat skin and greatly increase the skin permeability of SH; microneedle arrays provide an efficient and promising technology for transdermal drug delivery of SH.