Preparation, characterization, and anticancer effects of an inclusion complex of coixol with ß-cyclodextrin polymers.

CONTEXT: Coix [Coix lacryma-jobi L. var. mayuen (Roman.) Stapf (Poaceae)], a crop of medicinal and edible significance, contains coixol, which has demonstrated anticancer properties. However, the limited solubility of coixol restricts its potential therapeutic applications. OBJECTIVE: This study prepared a water-soluble coixol-ß-cyclodextrin polymer (CDP) inclusion compound and evaluated its anticancer effect. MATERIALS AND METHODS: The coixol-CDP compound was synthesized through a solvent-stirring and freeze-drying technique. Its coixol content was quantified using HPLC, and its stability was tested under various conditions. The anticancer effects of the coixol-CDP compound (4.129, 8.259, 16.518, and 33.035 mg/L for 24, 48, and 72 h) on the proliferation of non-small cell lung cancer (NSCLC) A549 cells were evaluated using an MTT assay; cell morphology was examined by Hoechst nuclear staining; apoptosis and cell cycle was detected by flow cytometry; and the expression of apoptosis-related proteins was assessed by Western blots. RESULTS: The water-soluble coixol-CDP inclusion compound was successfully prepared with an inclusion ratio of 86.6% and an inclusion yield rate of 84.1%. The coixol content of the compound was 5.63% and the compound remained stable under various conditions. Compared to coixol alone, all 24, 48, and 72 h administrations with the coixol-CDP compound exhibited lower IC50 values (33.93 ± 2.28, 16.80 ± 1.46, and 6.93 ± 0.83 mg/L) in A549 cells; the compound also showed stronger regulatory effects on apoptosis-related proteins. DISCUSSION AND CONCLUSIONS: These findings offer a new perspective for the potential clinical application of Coix in NSCLC therapy and its future research.

Fabrication and Characterization of Antifungal Hydroxypropyl-ß-Cyclodextrin/Pyrimethanil Inclusion Compound Nanofibers Based on Electrospinning.

Pyrimethanil (PMT) is an anilinopyrimidine bactericide with poor water solubility, which limits its applications. To improve the physical and chemical properties of PMT, hydroxypropyl-ß-cyclodextrin/pyrimethanil inclusion compound nanofibers (HPßCD/PMT-IC-NFs) were fabricated via electrospinning. A variety of analytical techniques were used to confirm the formation of the inclusion compound. Scanning electron microscopy image displayed that HPßCD/PMT-IC-NF was homogeneous without particles. Thermogravimetric analysis indicated that the formation of the inclusion compound improved the thermostability of PMT. In addition, the phase solubility test illustrated that the inclusion compound formed by PMT and HPßCD had a stronger water solubility. The antifungal effect test exhibited that HPßCD/PMT-IC-NF had better antifungal properties. The release experiment confirmed that HPßCD/PMT-IC-NF had a sustained-release effect, and the release curve conformed to the first-order kinetic model equation. In short, the fabrication HPßCD/PMT-IC-NF inhibited improved solubility and thermostability of PMT, thus promoting the development of pesticide dosage form to water-based and low-pollution direction.

Application of cyclodextrin in food industry.

Due to special cavity structure, cyclodextrin can form inclusion complex with a large number of compounds, which can be widely used in food industry, such as enhancing antibacterial activity, extending the storage period of food, increasing the solubility of food ingredients, removing cholesterol in food and so on. In this paper, the formation mechanism, classification and properties of cyclodextrin inclusion complex were reviewed, and the applications of cyclodextrin and its derivatives in food industry were discussed.

Diversity of N-triphenylacetyl-L-tyrosine solvates with halogenated solvents.

The structure of N-triphenylacetyl-L-tyrosine (C29H25NO4, L-TrCOTyr) is characterized by the presence of both donors and acceptors of classical hydrogen bonds. At the same time, the molecule contains a sterically demanding and hydrophobic trityl group capable of participating in π-electron interactions. Due to its large volume, the trityl group may favour the formation of structural voids in the crystals, which can be filled with guest molecules. In this article, we present the crystal structures of a series of N-triphenylacetyl-L-tyrosine solvates with chloroform, namely, L-TrCOTyr·CHCl3 (I) and L-TrCOTyr·1.5CHCl3 (III), and dichloromethane, namely, L-TrCOTyr·CH2Cl2 (II) and L-TrCOTyr·0.1CH2Cl2 (IV). To complement the topic, we also decided to use the racemic amide N-triphenylacetyl-DL-tyrosine (rac-TrCOTyr) and recrystallized it from a mixture of chloroform and dichloromethane. As a result, rac-TrCOTyr·1.5CHCl3 (V) was obtained. In the crystal structures, the amide molecules interact with each other via O-H...O hydrogen bonds. Noticeably, the amide N-H group does not participate in the formation of intermolecular hydrogen bonds. Channels are formed between the TrCOTyr molecules and these are filled with solvent molecules. Additionally, in the crystals of III and V, there are structural voids that are occupied by chloroform molecules. Structure analysis has shown that solvates I and II are isostructural. Upon loss of solvent, the solvates transform into the solvent-free form of TrCOTyr, as confirmed by thermogravimetric analysis, differential scanning calorimetry and powder X-ray diffraction.

Pharmacokinetics of five phthalides in volatile oil of Ligusticum sinense Oliv.cv. Chaxiong, and comparison study on physicochemistry and pharmacokinetics after being formulated into solid dispersion and inclusion compound.

BACKGROUNDS: The dried rhizome of Ligusticum sinense Oliv.cv. Chaxiong has been used to treat cardiovascular and cerebrovascular diseases, atherosclerosis, anemia and stroke. A high purity extract from chaxiong (VOC, brownish yellow oil) was extracted and separated. Its main components were senkyunolide A (SA, 33.81%), N-butylphthalide (NBP, 1.38%), Neocnidilide (NOL, 16.53%), Z-ligustilide (ZL, 38.36%), and butenyl phthalide (BP, 2.48%), respectively. Little is known about the pharmacokinetics of these phthalides in Chaxiong, and different preparations to improve the physicochemistry and pharmacokinetics of VOC have not been investigated. METHODS: At different predetermined time points after oral administration or intravenous administration, the concentrations of SA, NBP, NOL, ZL and BP in the rat plasma were determined using LC-MS/MS, and the main PK parameters were investigated. VOC-P188 solid dispersion and VOC-ß-CD inclusion compound were prepared by melting solvent method and grinding method, respectively. Moreover, the physicochemical properties, dissolution and pharmacokinetics of VOC-P188 solid dispersion and VOC-ß-CD inclusion compound in rats were assessed in comparison to VOC. RESULTS: The absorptions of SA, NBP, NOL, ZL and BP in VOC were rapid after oral administration, and the absolute bioavailability was less than 25%. After the two preparations were prepared, dissolution rate was improved at pH 5.8 phosphate buffer solution. Comparing VOC and physical mixture with the solid dispersion and inclusion compound, it was observed differences occurred in the chemical composition, thermal stability, and morphology. Both VOC-P188 solid dispersion and VOC-ß-CD inclusion compound had a significantly higher AUC and longer MRT in comparison with VOC. CONCLUSION: SA, NBP, NOL, ZL and BP in VOC from chaxiong possessed poor absolute oral bioavailability. Both VOC-P188 solid dispersion and VOC-ß-CD inclusion compound could be prospective means for improving oral bioavailability of SA, NBP, NOL, ZL and BP in VOC.

Crystal and molecular structure of V-amylose complexed with ibuprofen.

Rectangular V-amylose single crystals were prepared by adding racemic ibuprofen to hot dilute aqueous solutions of native and enzymatically-synthesized amylose. The lamellar thickness increased with increasing degree of polymerization of amylose and reached a plateau at about 7 nm, consistent with a chain-folding mechanism. The CP/MAS NMR spectrum as well as base-plane electron and powder X-ray diffraction patterns recorded from hydrated specimens were similar to those of V-amylose complexed with propan-2-ol. Amylose was crystallized in an orthorhombic unit cell with parameters a = 2.824 ± 0.001 nm, b = 2.966 ± 0.001 nm, and c = 0.800 ± 0.001 nm. A molecular model was proposed based on structural analogies with the Vpropan-2-ol complex and on assumptions on the stoichiometry of ibuprofen. The unit cell would contain four antiparallel 7-fold amylose single helices with ibuprofen molecules distributed inside and between the helices.

Nanocarriers and Microcarriers for Enhancing the UV Protection of Sunscreens: An Overview.

This review addresses a major question of importance to pharmaceutical scientists: how can novel drug delivery systems play a role in maximizing the UV protection of sunscreens? Because more and more people are being diagnosed with skin cancer each year than all other cancers combined, adequate sun protective measures are pivotal. In this context, the present review is to give an up-to-date overview on the different nanocarrier systems that have been explored so far for encapsulating different types of UV filters present on the market. The aim of these carrier systems is to prevent skin penetration and to enhance the photoprotective potential of sunscreen actives. For each supramolecular system, a brief description along with the studies, achievements, and pitfalls, on the type of UV actives inside them, ranging from classical UV filters to new generation of UV actives is given. A brief overview of UV filters encapsulated in microcarriers is also discussed.

Smart Molecular Recognition: From Key-to-Lock Principle to Memory-Based Selectivity.

The formation and decomposition of inclusion compounds with a solid-solid phase transition may be very selective to the guest molecular structure. This selectivity may function in essentially different ways than defined by the classical concept of molecular recognition, which implies the preferential binding of complementary molecules. Solid inclusion compounds may take part as an initial or/and final state in several processes of different types summarized in this review, which selectivity is boosted by cooperativity of participating molecular crystals. Some of these processes resemble switching electronic devices and can be called smart giving practically absolute molecular recognition.

Studies on high-efficiency loading, sustained-release and permeability as transdermal delivery of graphene oxide to docetaxel composites / 中草药

Objective: To synthetize the new-type GO-DEX-β-CD/DOC and Fe3O4/GO-Na/DOC inclusion compound, and study its high-efficiency loading, sustained-release and permeability as transdermal delivery for docetaxel (DOC) composites. Methods: The concentration of DOC was determined by high efficiency liquid chromatography. The high-efficiency loading, sustained-release and permeability as transdermal delivery of GO-DEX-β-CD/DOC and Fe3O4/GO-Na/DOC were studied, and the encapsulation efficiency and drug loading of them were determined by centrifugation. The GO-DEX-β-CD/DOC and Fe3O4/GO-Na/DOC were applied onto the female mice skin in vitro and in vivo to develop the permeability of them. Results: The encapsulation efficiency and drug loading of Fe3O4/GO-Na/DOC were higher than GO-DEX-β-CD/DOC, and its slow release property and permeability as transdermal delivery were better. The results showed that the accumulation permeation amount was (22.512 ± 0.715) μg after Fe3O4/GO-Na/DOC being applied over 90 h, DOC concentration in skin reached a peak at 15 min by the application of Fe3O4/GO-Na/DOC. After 5 h of administration, DOC concentration in the blood of female mice reached (76.886 ± 1.232) μg/mL. Conclusion: The preparation techniques of Fe3O4/GO-Na/DOC was feasible with better sustained release and transdermal effect, which had a promising application prospect.

Study on Preparation Phase Identification and Release Rate in vitro of Inclusion Compound of Indapamide- β-cyclodextrin Inclusion Compound / 中国药房

OBJECTIVE： To establish a method for content determination of indapamide （IDP）-β-cyclodextrin （β-CD） inclusion compound， optimize the preparation technology， carry out phase identification and in vivo release study of it. METHODS： UV spectrophotometry was used to determine the content of IDP in IDP-β-CD inclusion compound. IDP-β-CD inclusion compound was prepared by the solution-stirring method and the preparation technology was optimized by the orthogonal experiment using inclusion rate as index. The inclusion rate and drug-loading rate were compared between different drying methods. Phase identification of IDP-β-CD inclusion compound was verified by IR and DSC. The cumulative release rate of inclusion compound was tested by in vitro experiment. RESULTS： The linear range of concentration of IDP was 2.0-14.0 μg/mL （r＝0.999 7）. The quantitative limit and detection limit were 0.204， 0.067 μg/mL， respectively. RSDs of precision， stability and repeatability tests were all less than 2％. The recoveries range was 98.8％-101.8％（RSD＝1.10％，n＝6）. The optimum technology conditions were as follows the molar ratio of β-CD to IDP was 3 ∶ 1， the inclusion time was 3 h， and the stirring speed was 300 r/min. Average inclusion rate of IDP-β-CD inclusion compound was 72.81％. IR and DSC analysis showed that IDP and β-CD formed inclusion compound through physical interaction. After spray drying， the inclusion rate and drug-loading rate of IDP-β-CD inclusion compound were （60.96±0.25）％ and （4.18±0.12）％. After freeze-drying， the inclusion rate and drug-loading rate of IDP-β-CD inclusion compound were （77.31±0.51）％ and （5.31±0.27）％. Accumulative release rates of IDP， IDP-β-CD inclusion compound （by freeze-drying and spray drying） were 37.2％， 42.5％ and 81.9％ within 12 h， respectively. Compared with IDP raw material， accumulative release rate of IDP-β-CD inclusion compound increased significantly after spray drying. CONCLUSIONS： Established method is simple and accurate. The optimal preparation technology of inclusion compound is stable and feasible. IDP-β-CD inclusion compound is prepared successfully. The inclusion compound prepared by spray drying shows higher release rate.

Photothermally Controlled Methotrexate Release System Using ß-Cyclodextrin and Gold Nanoparticles.

The inclusion compound (IC) of cyclodextrin (CD) containing the antitumor drug Methotrexate (MTX) as a guest molecule was obtained to increase the solubility of MTX and decrease its inherent toxic effects in nonspecific cells. The IC was conjugated with gold nanoparticles (AuNPs), obtained by a chemical method, creating a ternary intelligent delivery system for MTX molecules, based on the plasmonic properties of the AuNPs. Irradiation of the ternary system, with a laser wavelength tunable with the corresponding surface plasmon of AuNPs, causes local energy dissipation, producing the controlled release of the guest from CD cavities. Finally, cell viability was evaluated using MTS assays for ß-CD/MTX and AuNPs + ß-CD/MTX samples, with and without irradiation, against HeLa tumor cells. The irradiated sample of the ternary system AuNPs + ß-CD/MTX produced a diminution in cell viability attributed to the photothermal release of MTX.

Composite host lattices of 4,4'-sulfonyldibenzoate water/boric acid in two tetrapropylammonium inclusion compounds.

Two novel inclusion compounds of 4,4'-sulfonyldibenzoate anions and tetrapropylammonium cations with different ancillary molecules of water and boric acid, namely bis(tetrapropylammonium) 4,4'-sulfonyldibenzoate dihydrate, 2C12H28N+·C14H8O6S2-·H2O (1), and bis(tetrapropylammonium) 4,4'-sulfonyldibenzoate bis(boric acid), 2C12H28N+·C14H8O6S2-·2H3BO3 (2), were prepared and characterized using single-crystal X-ray diffraction. In the two salts, the host 4,4'-sulfonyldibenzoic acid molecules, which are converted to the corresponding anions under basic conditions, can be regarded as proton acceptors which link different proton donors of the ancillary molecules of water or boric acid. In this way, an isolated hydrogen-bonded tetramer is constructed in salt 1 and a ribbon is constructed in salt 2. The tetramers and ribbons are then packed in a repeating manner to generate various host frameworks, and the tetrapropylammonium guest counter-ions are contained in the cavities of the host lattices to give the final stable crystal structures. In these two salts, although the host anion and guest cation are the same, the difference in the ancillary small molecules results in different structures, indicating the significance of ancillary molecules in the formation of crystal structures.

Evidence of hypoglycemic, lipid-lowering and hepatoprotective effects of the Bixin and Bixin: ß-CD inclusion compound in high-fat-fed obese mice.

Associations between obesity, diabetes type II, and steatosis have long been recognized. However, a pharmacotherapy that acts in a multifactorial manner controlling the interactions between these conditions is not available. A variety of natural plants, functional fatty acids, and other natural dietary compounds have been used in various anti-obesity products. We investigated the effects of oral administration of an antioxidant carotenoid pigment Bixin and Bixin: ß-Cyclodextrin in an obese murine model. C57BL/6 male mice (4-5 weeks) received standard diet (2.18 kcal per 1 g) (CT) and high-fat diet (4.38 kcal per 1 g) (CT/OB, BIX and BIX/ßCD) (n = 10 per group). After 16 weeks, the BIX and BIX/ßCD were treated by gavage (100 µL day-1) for six weeks, with water (CT and CT/OB groups) and (50 mg kg-1 day-1), Bixin (BIX group) or Bix: ß-CD (BIX/ßCD). Body weight, Lee's Index, adiposity, CHT, TG, CHT/HDL-c, glucose levels (metabolic markers) and, liver markers (AST and ALT) were determined. All metabolic and liver parameters exhibited down-regulation after oral administration of BIX and BIX/ßCD. Particularly relevant was Lee's Index and adiposity in BIX- and BIX/ßCD-treated groups (339.18 g/cm -BIX and 327.58 g/cm -BIX/ßCD vs. 360.68 g/cm -CT/OB animals), this finds associated with the insulin sensitivity test, showed a clear association between reduction of adipose tissue and decrease of peripherical insulin resistant. In conclusion, our study suggested that the oral administration of the Bixin and Bix: ß-CD inclusion compound improved the metabolic parameters evaluate in obese mice, being more palatable and hepatoprotective.

Crystal structure of a supra-molecular lithium complex of p-tert-butyl-calix[4]arene.

Crystals of a supra-molecular lithium complex with a calix[4]arene derivative, namely tetra-methano-llithium 5,11,17,23-tetra-tert-butyl-25,26,27-trihy-droxy-28-oxidocalix[4]arene methanol monosolvate, [Li(CH3OH)4](C44H55O4)·CH3OH or [Li(CH3OH)4]+·(calix[4]arene-)]·CH3OH (where calix[4]arene- represents a mono-anion species because of deprotonation of one H atom of the calixarene hy-droxy groups), were obtained from p-tert-butyl-calix[4]arene reacted with LiH in tetra-hydro-furan, followed by recrystallization from methanol. The asymmetric unit comprises one mono-anionic calixarene mol-ecule, one Li+ cation coordinated to four methanol mol-ecules, and one methanol mol-ecule included in the calixarene cavity. The calixarene mol-ecule maintains a cone conformation by intra-molecular hydrogen bonding between one phenoxide (-O-) and three pendent calixarene hy-droxy groups (-OH). The coordinated methanol mol-ecules around the metal cation play a significant role in forming the supra-molecular assembly. The crystal structure of this assembly is stabilized by three sets of inter-molecular inter-actions: (i) hydrogen bonds involving the -OH and -O- moieties of the calixarene mol-ecules, the -OH groups of the coordinated methanol mol-ecules, and the -OH group of the methanol mol-ecule included in the calixarene cavity; (ii) C-H⋯π inter-actions between the calixarene mol-ecules and/or the coordinated methanol mol-ecules; (iii) O-H⋯π inter-actions between the calixarene mol-ecule and the included methanol mol-ecule.

A long-lasting oral preformulation of the angiotensin II AT1 receptor antagonist losartan.

Losartan (Los), a non-peptidic orally active agent, reduces arterial pressure through specific and selective blockade of angiotensin II receptor AT1. However, this widely used AT1 antagonist presents low bioavailability and needs once or twice a day dosage. In order to improve its bioavailability, we used the host: guest strategy based on ß-cyclodextrin (ßCD). The results suggest that Los included in ßCD showed a typical pulsatile release pattern after oral administration to rats, with increasing the levels of plasma of Los. In addition, the inclusion compound presented oral efficacy for 72 h, in contrast to Los alone, which shows antagonist effect for only 6 h. In transgenic (mREN2)L27 rats, the Los/ßCD complex reduced blood pressure for about 6 d, whereas Los alone reduced blood pressure for only 2 d. More importantly, using this host: guest strategy, sustained release of Los for over a week via the oral route can be achieved without the need for encapsulation in a polymeric carrier. The proposed preformulation increased the efficacy reducing the dose or spacing between each dose intake.

Green options for imparting antibacterial functionality to cotton fabrics.

This study demonstrated that antibacterial cellulosic textiles can be fabricated in eco-friendly manner by grafting of monochlorotriazinyl ß-cyclodextin (MCT-ßCD) onto knitted and woven cotton fabrics followed by post-loading of any of the green active ingredients namely Rosemary oil, Lavender oil, Clove oil, Cinnamon oil, Aloe vera gel, Vanillin, Ag-ions, Natural Yellow 7 and Natural Red 25 dyes into the hydrophobic cavities of grafted ß-CD moieties. Some of the grafted, post-loaded fabric samples were characterized by FTIR, SEM, and EDS analysis. The enhancement in the imparted antibacterial functionality as well as durability to wash are governed by type of cellulosic substrate, kind, chemistry, antibacterial activity as well as extent of inclusion and subsequent release of the hosted bioactive agent. The obtained results revealed that the antibacterial efficacy follows the deceasing orders: i) knitted fabric > woven fabric and ii) Ag-ions > Lavender oil > Natural Yellow 7 > Aloe vera > Cinnamon oil > Natural Red 25 > Vanillin > Clove oil > Rosemary oil-loaded fabric sample, keeping other parameters constant.

Comparison of a revaprazan-loaded solid dispersion, solid SNEDDS and inclusion compound: Physicochemical characterisation and pharmacokinetics.

The aim of this research was to compare three strategies for enhancing the solubility of poorly water-soluble revaprazan hydrochloride: solid dispersion, solid SNEDDS and inclusion compound. The influence of polymers, surfactants and oils on the drug solubility was assessed, and via the chosen carriers, the three types of formulations were prepared utilising spray drying technique. Their physicochemical properties, solubility, dissolution and pharmacokinetics in rats were performed compared with revaprazan powder. Among the liquid SNEDDS formulations assessed, the compositions of revaprazan, peceol, Tween 80 and Labrasol (10:15:55:30, weight ratio) provided the smallest emulsion size. Moreover, this liquid SNEDDS and dextran were suspended/dissolved in distilled water, and spray-dried, producing an optimal revaprazan-loaded solid SNEDDS. The appropriate solid dispersion and inclusion compound were composed of revaprazan, hydroxypropylmethylcellulose and cremophor A25 (5:1.4:5.6) and drug and hydroxyl-ß-cyclodextrin (2.5:8.77), respectively. The crystalline drug was converted to an amorphous state in all formulations. In the solid dispersion, the drug was attached to the hydrophilic carrier. The solid SNEDDS and inclusion compound contained aggregate microspheres and separate microspheres, respectively. All formulations significantly increased the drug solubility, dissolution, plasma concentration and AUC compared with revaprazan powder. These properties were ranked in the order solid dispersion ≥ solid SNEDDS > inclusion compound. Particularly, the solid dispersion improved about 9500-fold drug solubility and 10-fold oral bioavailability. Thus, the improved properties were considerably dependent upon these techniques, although all of the techniques employed similar mechanisms. Among the strategies checked, the solid dispersion system would be recommended as an oral revaprazan-loaded pharmaceutical product.

Effects of Cyclodextrin Inclusion on the Degradation of Tanshinone ⅡA in Rat Intestinal Flora / 中国药学杂志

OBJECTIVE: To observe effects of β-cyclodextrin inclusion on tanshinone ⅡA in the degradation which in rat intestinal flora in vitro. METHODS: Culturing the tanshinone ⅡA and inclusion compound separately with incubation buffer of rat intestinal flora, sampling after 06121824 h. Extracting the sample then analyze content by HPLC. RESULTS: The tanshinone ⅡA is degraded obviously by rat intestinal flora in vitro and degradation speed became slower after forming the inclusion compound. After degrading 18 h, the declining proportion of tanshinone ⅡA concerntration which in tanshinone ⅡA group and mixture of tanshinone ⅡA with β-cyclodextrin group reached (74.23±2.32)% and (80.23±1.14)% while (47.45±4.01)% in β-cyclodextrin inclusion group. CONCLUSION: The tanshinone ⅡA is degraded almost completely by rat intestinal flora in vitro during 24 h, the degradation speed will be slower while forming the inclusion compound.

Preparation and Quality Evaluation of Formononetin Inclusion Compound Liposome / 中国药房

OBJECTIVE: To prepare Formononetin (FMN) inclusion compound liposome and evaluate its quality. METHODS: FMN inclusion compound liposome was prepared by film dispersion method. The morphology, particle size, Zeta potential, encapsulation efficiency and in vitro release properties were studied. RESULTS: The particle size, Zeta potential and encapsulation efficiency of prepared FMN inclusion compound liposome were (255. 34 ± 12. 87) nm, (25. 32 ± 3. 51) mV, (81. 63 ± 0. 79)％, respectively (n=3). The 24 h accumulative release rate of prepared FMN inclusion compound liposome was 56. 12％. CONCLUSIONS: FMN inclusion compound liposome with good sustained-release effect is prepared successfully and in line with related quality standard.

Preparation of thermosensitive intestinal gels of Houttuynia cordata volatile oils HPCD inclusion compound / 中成药

AIM To prepare the thermosensitive intestinal gels of Houttuynia cordata Thunb volatile oils hydroxypropyl-β-cyclodextrin (HPCD) inclusion compound.METHODS For the gels prepared by cold dissolving method,poloxamer 407 consumption and poloxamer 188 consumption were taken as influencing factors,together with phase transition temperature as an evaluation index,central composite design-response surface method was applied to optimizing the formulation.With 2-undecanone as an index component,the gels' dissolution rate and in vitro release rate were investigated by non-membrane dissolution method and dialysis bag method respectively,whose stability was then evaluated by high temperature (40,60 ℃),low temperature (4 ℃),strong light [(4 500 ±500) 1x] and acceleration (three months) tests.RESULTS The optimal conditions were determined to be 20.61％ for P407 consumption and 3.03％ for P188 consumption,the phase transition temperature was 36.5 ℃.Within the time range of 30-150 min,the HPCD inclusion compound gels exhibited higher accumulative dissolution rate than the volatile oils gels,which tended to be consistent in 150-210 min,but the former exhibited higher accmulative release rate (0-50 h) than the latter all the time.The obtained gels showed good stability at low temperature,whose appearance,characteristic (except for high temperature) and pH were stable at high temperature,strong light and acceleration with obviously decreased 2-undecanone content.CONCLUSION The thermosensitive intestinal gels of Houttuynia cordata Thunb volatile oils HPCD inclusion compound should be stored at low temperature (4 ℃).