Theoretical insights and implications of pH-dependent drug delivery systems using silica and carbon nanotube.

In this paper we have studied the density functional theory of four drugs ibuprofen, alendronate, Sulfasalazine and paracetamol with quartz, propylamine, trimethylamine functionalized quartz and carboxyl modified carbon nanotube. The attractive and repulsive interaction energies between drugs and quartz is obtained at various pH values. The attractive and repulsive energies are well correlated with experimental drug loading and releasing behavior by mesoporous silica nanoparticles. Further, a theoretical model is developed that accounts the electrostatic interaction between silica and drug and the model can predict the drug loading and releasing behavior by silica nanoparticles at various pH values. Sulfasalazine can be taken orally and loaded with trimethyl ammonium functionalized mesoporous silica nanoparticles, which keeps the drug in tact with the carrier in the acidic environment of the stomach and releases it into the neutral or basic medium of the small intestine. Alendronate may be loaded and released from propylamine functionalized mesoporous silica nanoparticles in the ranges of 1-5 and > 8, respectively. Ibuprofen is absorbed in an acidic environment and released in basic conditions for carboxyl modified carbon nanotube. The loading and releasing pH ranges for paracetamol in trimethylammonium functionalized mesoporous silica nanoparticles are 4-8 and >8, respectively. We also convert the pH-dependent variant of the diffusion-controlled Higuchi equation. We have changed the original Higuchi equation to produce the pH-dependent variation by incorporating the Nernst-Planck equation into Flick's first law. The updated equation could be used to forecast when medication particles with varying release times will emerge from a nanoparticles matrix.

Design of a pH-responsive oral gel formulation based on the matrix systems of gelatin/hydroxypropyl methylcellulose phthalate for controlled drug release.

Extensive efforts have been directed toward developing novel easily digested formulations with desirable controlled-release properties. The present study sought to develop pH-responsive oral gel formulations using combinations of gelatin and enteric polymers for controlled drug release under stimulated gastric conditions using acetaminophen and fluorescein isothiocyanate (FITC)-labeled dextran as model compounds. Hydroxypropyl methylcellulose phthalate (HPMCP) was identified as the optimal excipient for the pH-responsive drug release system because the release rates of acetaminophen in gelatin/HPMCP gels at pH 1.2 were exceedingly lower than those in other polymer-containing gels. Texture profile analysis of gelatin/HPMCP gels revealed the optimal content of excipients concerning ingestibility. FITC-labeled dextran of varying molecular weights was used to investigate the mechanism of compound release from the gelatin/HPMCP system under acidic conditions. The release properties practically depended on the molecular weight of FITC-dextran, and the compound release rate was proportional to the square root of time. The matrix structures of gelatin/HPMCP gels at low pH offer advantageous pH-responsive drug release profiles.

[Preparation and evaluation of four kinds of mixed essential oil liposomes in Jieyu Anshen Formula].

In order to increase the stability and solubility of essential oil in Jieyu Anshen Formula, this study was to prepare the essential oil into liposomes. In this experiment, the method for the determination of encapsulation efficiency of liposomes was established by ultraviolet spectrophotometer and dextran gel column. The encapsulation efficiency and particle size of liposomes were used as evaluation indexes for single factor investigation and Box-Behnken design-response surface method was used to optimize the design. Then the optimal formulation of volatile oil liposome was characterized using methyleugenol, elemin, ß-asarone and α-asarone as index components. Finally, the in vitro transdermal properties of liposomes were studied by modified Franz diffusion cell. The results showed that the concentration of lecithin, the mass ratio of lecithin to volatile oil, and the stirring speed were the three most significant factors affecting the liposome preparation. The optimum formulation of volatile oil liposome was as follows: the concentration of lecithin was 7 g·L~(-1); mass ratio of lecithin to volatile oil was 5∶1; and the stirring speed was 330 r·min~(-1). Under such conditions, the prepared liposomes had blue emulsion light, good fluidity, half translucent, with particle size of(102.6±0.35) nm, Zeta potential of(-17.8±0.306) mV, permeability of(1.67±1.01)%, and stable property if liposome was stored at 4 ℃. 24 h after percutaneous administration, the cumulative osmotic capacity per unit time was(30.485 2±1.238 9),(34.794 8±0.928 3),(26.677 1±1.171 7),(3.066 2±0.175 3) µg·cm~(-2)respectively for methyleugenol, elemin, ß-asarone and α-asarone. In vitro transdermal behaviors of methyleugenol, elemin, ß-asarone and α-asarone in liposomes were all consistent with Higuchi equation. The prepared volatile oil liposomes met the relevant quality requirements, providing a reference for further research on preparation of multi-component Chinese medicine essential oil liposomes.

Preparation and evaluation of four kinds of mixed essential oil liposomes in Jieyu Anshen Formula / 中国中药杂志

In order to increase the stability and solubility of essential oil in Jieyu Anshen Formula, this study was to prepare the essential oil into liposomes. In this experiment, the method for the determination of encapsulation efficiency of liposomes was established by ultraviolet spectrophotometer and dextran gel column. The encapsulation efficiency and particle size of liposomes were used as evaluation indexes for single factor investigation and Box-Behnken design-response surface method was used to optimize the design. Then the optimal formulation of volatile oil liposome was characterized using methyleugenol, elemin, β-asarone and α-asarone as index components. Finally, the in vitro transdermal properties of liposomes were studied by modified Franz diffusion cell. The results showed that the concentration of lecithin, the mass ratio of lecithin to volatile oil, and the stirring speed were the three most significant factors affecting the liposome preparation. The optimum formulation of volatile oil liposome was as follows: the concentration of lecithin was 7 g·L~(-1); mass ratio of lecithin to volatile oil was 5∶1; and the stirring speed was 330 r·min~(-1). Under such conditions, the prepared liposomes had blue emulsion light, good fluidity, half translucent, with particle size of(102.6±0.35) nm, Zeta potential of(-17.8±0.306) mV, permeability of(1.67±1.01)%, and stable property if liposome was stored at 4 ℃. 24 h after percutaneous administration, the cumulative osmotic capacity per unit time was(30.485 2±1.238 9),(34.794 8±0.928 3),(26.677 1±1.171 7),(3.066 2±0.175 3) μg·cm~(-2)respectively for methyleugenol, elemin, β-asarone and α-asarone. In vitro transdermal behaviors of methyleugenol, elemin, β-asarone and α-asarone in liposomes were all consistent with Higuchi equation. The prepared volatile oil liposomes met the relevant quality requirements, providing a reference for further research on preparation of multi-component Chinese medicine essential oil liposomes.

Preparation and evaluation of triptolide and ferulic acid ethosomes / 中草药

Objective In order to optimize the preparation technology of triptolide and ferulic acid ethosomes and evaluate its characteristics of the in vitro transdermal penetration and the preparations performance using ethosome as carrier. Methods The compatibility ratio between triptolide and ferulic acid was determined by MTT. The triptolide and ferulic acid ethosomes were prepared with injection method based on the results of single factor experiments, Box-Behnken design was used to optimize the particle size, electric potential, and encapsulation efficiency (EE) of the ethosomes, and the in vitro release behavior prepared by the optimal formulation were studied. The in vitro transdermal absorption experiment was carried out in optimized Franz diffusion cells. Results The ratio of triptolide to ferulic acid was 1:100. The optimized prescription of the ethosomes was 20% ethanol, 2.2% phospholipid, 90 s ultrasonic time. The results showed that the appearance of the triptolide and ferulic acid ethosomes was clear liquid with blue opalescence in an average diameter of (46.75 ± 2.39) nm at potential of (-46.32 ± 3.76) mV, and the EE was (67.72 ± 1.10)%. The in vitro transdermal behaviors of ferulic acid and triptolide in the ethosomes were in line with the Higuchi equation. Conclusion The ethosomes has the advantages of small particle size, uniform distribution, good stability, and good transdermal absorption property, so as to provide the basis for the development of the transdermal preparation of the effective components of Tripterygium wilfordii.

Assessment of the usage of biodegradable polymeric matrix in vaginal devices to sustain progesterone release in cows.

The usage of timed artificial insemination (TAI) at a low cost leading to better reproductive rates has been the aim of several research groups in the field. Usually during TAI protocols, sustained progesterone (P4 ) release devices are employed. Most devices are constituted of a nylon skeleton covered with a silicon layer with P4 . A device based on biopolymers was developed in order to reduce costs and decrease its environmental impact. In this study, we compared the kinetics of sustained progesterone release among devices manufactured with a polymeric blend made of polyhydroxybutyrate-valerate (PHBV) and poly-ε-caprolactone (PCL) (DISP) which were compared with DIB® (Internal Bovine Device) used as the control. In the in vitro and in vivo progesterone release tests, two types of biopolymer-based devices with a superficial area of 147 cm2 were used: DISP8 (46% PHBV, 46% PCL and 8% P4 ; n = 4), DISP10 (45% PHBV, 45% PCL, 10% P4 ; n = 4) and DIB® (1 g P4 , 120 cm2 area; n = 3). The in vitro tests were carried out according to USP XXIII specifications and were performed in a dissolutor sink using an alcohol/water mixture (60/40 v/v) as a release media and samples were collected at 2 min, 2, 4, 8, 12, 24, 48, 60, 72, 84 and 96 h. P4 concentrations were measured through spectrophotometry in a 244 nm long wave. Three to 3 comparisons of angular coefficients of the straight lines obtained by regression analysis of accumulated P4 concentrations as a function of square root of time were carried out. Furthermore, the diffusion coefficient values of P4 were also determined for DISP8 and DISP10. The results showed that the concentrations of P4 were higher in the DISP10 (774.63 ± 45.26 µg/cm2 /t1/2 ) compared to DISP8 (566.17 ± 3.68 µg/cm2 /t1/2 ) (P < 0.05). However, both DISP10 and DISP8 P4 concentrations did not differ from DIB® (677.39 ± 16.13 µg/cm2 /t1/2 ). For the analysis of released quantities per day of the in vitro test, four periods were considered: 0-24, 24-48, 48-72 and 72-96 h. In the first 24 h, DISP8 released significantly less P4 than DISP10 or DIB®, which did not differ among them. Between 24 and 48 h, DISP10 released significantly more P4 than DIB®. DISP8 released an intermediate P4 amount and did not differ significantly from DIB® or DISP10. Between 48 and 72 h, P4 quantity released by DISP10 was significant higher (P < 0.01) than that of DIB® and DISP8, which did not differ among themselves. Between 72 and 96 h, DISP10 released significantly more P4 than DIB®, and DISP8 released an intermediate amount which did not differ from DIB® or DISP10 (P < 0.01). There was interaction between treatment and time (P = 0.0024). The diffusion coefficient values were: 1.36 × 10-8 (cm2 /s) for DISP10 and 1.12 × 10-8 (cm2 /s) for DISP8. For the in vivo test, ovariectomized crossbred cows received DIB® (n = 4) or DISP8 (n = 8) in an alternate design with a non-balanced sequence (cross-over) added of measures repeated in time referring to 16 days of blood samples collection. Samples were analyzed through radioimmunoassay in solid phase using the commercial kit of DPC (Diagnostics Products Corporation). Plasma concentrations of P4 peaked at 4 h after the placement of the device, this being the only time in which plasma P4 concentrations differed between DIB® (11.45 ± 1.96) compared with DISP8 (9.23 ± 1.15 ng/mL) (P = 0.027). On day 8, plasma P4 concentrations were similar for DIB® (2.44 ± 0.09) and DISP8 (1.89 ± 0.13 ng/mL) (P = 0.58) showing that both devices were able to keep P4 concentrations above 1 ng/mL in the plasma of the cow during the 16 day in vivo test. In conclusion, devices manufactured with the blend of PHBV/PCL biopolymers can sustain the release of P4 in a similar manner as silicon.

Formulation and quality determination of indapamide matrix tablet: a thiazide type antihypertensive drug.

PURPOSE: The present study was explored to develop a sustained release matrix tablet of Indapamide, a low-dose thiazide-type diuretic, using hydroxylpropyl methylcellulose (Methocel K15MCR) in various proportions as release controlling factor. METHODS: The tablets were formulated using direct compression method. The powers for tableting were evaluated for angle of response, loose bulk density, tapped bulk density, compressibility index, total porosity and drug content etc. The tablets were subjected to thickness, weight variation test, drug content, hardness, friability, and in vitro dissolution studies. RESULTS: The granules showed satisfactory flow properties, compressibility index, and drug content. All the formulated tablets complies pharmacopoeia specifications. The release kinetics of the drug decreased exponentially with the addition of polymer concentration. Indapamide release rate was observed to be the highest with the lowest concentration of polymer used. The release mechanism was explored with zero order, first order, Higuchi and Krosmeyer equations. Stability tests of the drug showed no notable changes in the rate of drug release, related substances and drug content. CONCLUSION: In the context, it can be suggested that this formulation of sustained release Indapamide tablets can be marketed to treat patients with hypertension ensuring proper healthcare.

Preparation of ethosomes-based gel of demethylzeylasteral and its transdermal behavior in vitro / 中草药

Objective: To prepare the ethosomes-based gel of demethylzeylasteral (DMZ) and to investigate its properties and transdermal absorption behavior. Methods: The infusion method was used to prepare DMZ ethosomes. The particle size, entrapment efficiency (EE), analysis methodology, and in vitro release behavior were examined, respectively. The in vitro transdermal absorption of ethosomes-based gel of DMZ was evaluated by Franz diffusion cells. Results: The DMZ ethosomes was yellowish emulsion. The average particle size of the ethosomes was (365.2 ± 14.4) nm and the EE was (72.30 ± 2.31)%. The cumulative permeation curve of DMZ in ethosomes-based gel was consistent with Higuchi equation (Q=80.198 t1/2-71.641, r=0.986 8). Compared with common gel, the ethosomes-based gel had 3.94 times higher cumulative permeation amount in 24 h. Conclusion: The prepared ethosomes- based gel of DMZ could enhance the transdermal permeation, which provides evidence for the development of transdermal drug delivery system of DMZ.

A Study on Releasing Rule of Artesunate TDD System / 中成药

Objective: To study the releasing rule of Artesunate TDD s (ASTDDs). Methods: To prepare the ASTDDS and determine the content of artesunate, the transdermal experiments are used to study the relation between accumulative releasing ratio or releasing speed and releasing time. Results: The content of artesunate is about 45mg/10cm 2 and the accumulative releasing ratio increases with releasing time, but releasing speed is constant when the releasing speed reached some value. Conclusion: The releasing rule of ASTDDs conforms to Higuchi equation. The ASTDDs can come to durable effect.