Quality control and drug-drug interactions between commercially available Metoprolol and Glimepiride tablets

Abstract Quality is paramount and needs to be maintained throughout the shelf life of pharmaceuticals. The current study aimed to evaluate the quality, potency, and drug-drug interaction in an in vivo animal model by using two drugs, namely, metoprolol and glimepiride. Tablets were selected for their physical characteristics, such as shape, size, and color. Quality control tests, such as weight variation, hardness, friability, and disintegration tests, and invitro drug release studies were performed as per USP. Drug-drug interaction and in vivo studies were carried out according to the standard protocol of the animal ethics committee. Quality control tests of both the tablets were within the specified range. The cumulative release percentages of the drugs were 81.12% and 85.36% for Metoprolol Tartrate and Glimepiride, respectively, in a physiological buffer solution within 1 h. The combination of metoprolol and Glimepiride also significantly decreased the blood glucose level in diabetic animals. However, the blood glucose level increased in the group receiving metoprolol only, but the difference was not significant. The result suggested that the formulations are safe. However, the chronic use of this combination requires frequent monitoring of blood glucose level to improve its efficacy and for the patient's safety.

Design of experiments assisted the development of inclusion complexes of ramipril using hydrophilic carriers for enhancement of solubility and dissolution rate

Abstract The goal of the present study was to develop inclusion complexes and polymers dispersions of ramipril prepared by physical mixing, kneading, co-evaporation, and solvent evaporation methods to enhance drug solubility and dissolution rate, and thereby to reduce drug dose and side effects using selected hydrophilic carriers such as β-CD, PVP-K25, PEG 4000, and HPMC K100M. The prepared formulations were characterized for solubility and in-vitro drug release studies. The systematic optimization of formulations was performed using I-Optimal experimental design by selecting factors such as type of carriers (X1), drug: carrier ratio (X2), and method of preparation (X3), and response variables including percent yield (Y1), solubility (Y2), Carr's index (Y3) and drug release in 30 min (Y4). Mathematical modeling was carried out using a quadratic polynomial model. The inclusion complex formulation (F27) was selected as an optimized batch by numerical desirability function and graphical optimization with the help of design space. The inclusion complex prepared by the co-evaporation method showed maximum drug solubility and released in pH 6.8 phosphate buffer compared to pure and other formulations. The inclusion complex is a feasible approach to improve the solubility, dissolution rate, bioavailability, and minimization of drugs' gastrointestinal toxicity upon oral administration of ramipril.

Preparation and in-vitro drug release of Baizhu Huanglian pellets containing colon-targeting capsules / 药学实践杂志

Objective Colon-targeting capsules based on gastric pellets and enteric pellets were prepared from Baizhu Huanglian prescription. The formulation composition and preparation process were optimized and the in-vitro release characteristics were investigated. Methods Optimum formulation composition and process parameters of Baizhu Huanglian pellets were screened out by single factor experiment and orthogonal design. The pellets core were prepared by extrusion-spheronization technique and coated in the fluid bed using bottom spray coating technique. To investigate the effect of coating level of the isolation layer, the proportion of polymer, the amount of plasticizer and weight gain of enteric coating on the release behavior of the enteric pellets. The pellets release behavior was fitted by model as well. Results The prescription of gastric pellets was drug loading 50%, PVPP 5%, MCC to lactose 1∶2 and wetting agent 40%. The process parameters were extrusion frequency 20 Hz, rounding speed 500 r/min and rounding time 5 min. The prescription of enteric pellets was drug loading 27%, PVPP 5%, MCC to lactose 5∶2, wetting agent 30% and adhesive 20%. The process parameters were extrusion frequency 20 Hz, rounding speed 700 r/min and rounding time 7 min. For enteric coating layer, the coating mixture of EUDRAGIT®L30D-55 to EUDRAGIT® FS30D was 1∶2. The amount of plasticizer was 10%. The increased weight of coating layer was 15%. The release time of enteric pellets in-vitro was up to 24 hours. The release behavior of the pellets conforms to the Higuchi model. Conclusion The colon targeting capsule of Baizhu Huanglian pellets were successfully prepared and showed the characteristics of sustained release and colon targeting.

Preparation and in vitro Release Property Study of Curcumin Dry Powder Inhalation Loaded by Nanoporous Flower-shaped Lactose / 中国药房

OBJECTIVE：To preparea novel Curcumin （Cur）dry powder inhalation （DPI）loaded by nanoporous flower-shaped lactose（FL），and to provide a safe and effective intrapulmonary drug delivery method for the therapy of chronic obstructive pulmonary disease with insoluble drugs. METHODS ：FL-loaded Cur （Cur-FL） compound powder was prepared by solution adsorption method. Using drug-loading amount and adsorption rate as indicators ，single-factor experiment was used to optimize Cur concentration，Cur-FL ratio （m/m）and adsorption time so as to determine the optimal preparation technology for Cur-FL compound powder. Fourier transform infrared spectroscopy ，scanning electron microscope and differential scanning calorimetry were used to characterize the physical and chemical properties of Cur-FL compound powder prepared with optimal technology. The water content and aerodynamic properties were determined ；in vitro drug release behavior was investigated by simulating the environment of artificial lung fluid. RESULTS ：The optimal preparation technology of Cur-FL compound powder was Cur concentration of 5 mg/mL，Cur-FL ratio of 1 ∶ 4，adsorption time of 1 h. The drug-loading amount of compound powder was （23.37±0.43）％，the encapsulation rate was （91.64±0.44）％，and the adsorption rate was （30.50±0.72）％. Cur-FL particles were flower shaped ；Cur was physically adsorbed in the pores of FL without chemical changes. The bulk density of Cur-FL compound was （0.21±0.02） g/cm3，tap density was （0.33±0.01）g/cm3，angle of repose was（24.07±0.31）°，average particle size was （3.96±0.80） μm，aerodynamic particle size was （3.33±0.99）μm，water content was （5.63 ±0.24）％，emptying rate was （92.53± 0.87）％，and deposition rate of effective parts in vitro was son- （45.93 ± 1.77）％ . Its 24 h solubility in artificial lung gwen.tan@csu.edu.cn fluid [（358.93±1.67）μg/mL] were 3.28 times of Cur ，48 h cumulative release ratesin in vitro （90.21％）were 1.63 times of Cur ，but Cur+FL physical mixture could not improve the solubility and release of Cur in artificial lung fluid. CONCLUSIONS ：Cur-FL compound powder has good in vitro release property ，and its powder properties ，solubility，water content ，fluidity and aerodynamic properties meet the requirements of DPI in Chinese Pharmacopoeia.

Preparation and in vivo and in vitro Characteristic Evaluation of Ligustrazine Ophthalmic Liposome Thermosen- sitive Gel / 中国药房

OBJECTIVE：To prepare Liguatrazine opthalmic liposome therm osensitive gel ，and to investigate its in vivo and in vitro characteristics. METHODS ：The ammonium sulfate gradient method was used to prepare Liguatrazine liposomes. The preparation technology was optimized by using orthogonal test. Using poloxamer P 407 as gel matrix ，Liguatrazine liposomes were prepared into thermosensitive gel. A membraneless model was used to study the dissolution and in vitro drug release of the gel. The modified Franz diffusion cell was used to investigate corneal permeability and further determine corneal hydration value. The effects of the gel on the proliferation of human corneal epithelial cell HCE-T. HE staining and Draize test were used to investigate the stimulatory effects of the gel on corneal cells of the rabbit ，and the histological changes of the eyes were observed. RESULTS ：The optimal preparation technology of Liguatrazine liposome was drug-lipid ratio of 1 ∶ 10（m/m），the ammonium sulfate concentration of 0.2 mol/L，phospholipid-cholesterol ratio of 4∶1（m/m），incubation temperature of 45 ℃. Then ligustrazine opthalmic liposome thermosensitive gel was prepared with 23％ poloxamer P 407 as gel matrix. The gel had good gelatinization temperature. The in vitro drug release and dissolution showed zero-order kinetic characteristics ，and in vitro drug release of the gel was mainly related to dissolution （R2＝0.993 4）. The cumulative transcorneal permeability of the gel was 43.3％ within 6 hours and corneal hydration value was 72.98％. Low and medium concentrations （1，5 mg/L）of Ligustrazine opthalmic liposome thermosensitive gel had no obvious proliferation toxicity to HCE-T cells ，but it showed cytotoxicity at high concentration （10 mg/L）. The mean Draize eyeirritation score of the gel on rabbit cornea was within non-stimulation，and there was no abnormal change in rabbit （No.2018001） corneal histology. CONCLUSIONS ： Prepared Ligustrazine opthalmic liposome thermosensitive gel has a suitable phase transition temperature ，good corneal permeability ，and low corneal irrit ation.

Study on Preparation and Related Properties of Diacerein-loaded PLGA Microspheres for Intra-articular Injection / 中国药房

OBJECTIVE:To prepare Diacerein (DCR)-loaded (poly lactic-co-glycolic acid) PLGA microspheres for intra-articular injection and investigate its related properties. METHODS:PLGA was used as microspheres material,and the microsphere was prepared by emulsification solvent evaporation method. The contents of DCR-PLGA microspheres were determined by HPLC,and drug-loading amount and entrapment efficiency were also calculated. Using entrapment efficiency as evaluation index,the preparation technology was optimized by orthogonal test. The morphology and particle size of microspheres were observed by optical microscope and SEM. Accumulative release rate was investigated by using in vitro release test. RESULTS:The linear range of DCR was 2.1-105.0 μg/mL(r＝0.999 9). RSDs of precision,stability,reproducibility and recovery tests were all lower than 2.0%. The optimal technology was PLGA concentration of 200 mg/mL,volume ratio of oil-water 1∶50,polyvinyl alcohol concentration of 1%. The prepared DCR-PLGA microspheres were spherical,average particle size was(11.2±4.7)μm, drug-loading amount was(4.25 ± 0.26)% and encapsulation rate was(92.30 ± 1.93)%,respectively. The drug release rate of DCR-PLGA microspheres within 360 h was about(73.08 ± 5.33)%. CONCLUSIONS:DCR-PLGA microspheres are prepared successfully with good morphology,suitable particle size and obvious sustained release effect,which are suitable for intra-articular injection.

Study on Optimization of Formulation Matrix of Processed Aconitum carmichaelii Hydrogel Patch and Its in vitro Drug Release / 中国药房

OBJECTIVE:To optimize formulation matrix of processed Aconitum carmichaelii hydrogel patch,and to investigate its in vitro drug release.METHODS:The ratio of NP700,dihydroxyaluminum aminoacetate,tartaric acid and PVP K90 in processed A.carmichaelii hydrogel patch matrix was optimized by central composite design-response surface method (CCD-RSM) with initial adhesion,peel strength and sensory evaluation as evaluation indexes.The modified Franz diffusion cell method was used for in vitro drug release test processed A.carmichaelii hydrogel patch using accumulative release amount of six ester type alkaloids benzene [benzoyl mesaconine (BM),benzoyl aconitum (BA),benzoylhy paconine (BH),mesaconitine (MT),hypaconitine (HT) and aconitine (AT)] as evaluation indexes.RESULTS:The optimal matrix formulation was NP700-dihydroxyaluminum aminoacetate-tartaric acid-PVP K90 (1.72 ∶ 0.10 ∶ 0.02 ∶ 1.65,m/m/m/m).In validation test,the contents of six ester type alkaloids were 52.77,28.52,28.78,8.81,8.75,8.21 μg/g(RSD＜5％,n=3),comprehensive score was 118.67 ± 1.33 (RSD=4.62％,n=3).The release behavior of BM in vitro conformed to the Higuchi equation.The release behaviors of other 5 alkaloids were consistent with the Higuchi equation.12 h accumulative release amounts of BM,BA,BH,MT,HT and AT were 12.04,2.95,3.55,2.64,2.48,1.97 μg/cm2,respectively.CONCLUSIONS:The processed A.carmichaelii hydrogei patch prepared by matrix prescription is good in appearance,adhesion and in vitro release.The research can provide a basis for the development of new dosage form of processed A.carmichaelii.

Preparation of thermo-sensitive diammonium glycyrrhizinate binary liposome gel and the in vitro drug-release behaviors / 中成药

AIM To prepare thermo-sensitive diammonium glycyrrhizinate binary liposome gel and to evaluate the in vitro drug-release behaviors.METHODS Cold dissolution method was adopted in the preparation of gel.With gel transition temperature as an evaluation index,amounts of Poloxamer 407 (P407),Poloxamer 188 (P188) and polysaccharides from Bletillae Rhizoma as influencing factors,central composite design-response surface method was applied to optimizing the formulation.Then the in vitro drug-release behaviors were evaluated by HPLC and Franz vertical diffusion cell method.RESULTS The optimal formulation was determined to be 18％ for P407 amount,4％ for P188 amount,and 0.6％ for polysaccharides' amount,the gel transition temperature was (37.5 ± 0.3) ℃.The accumulative release rate of obtained thermo-sensitive binary liposome gel was (65.52 ± 0.63) ％ within 48 h,which showed more obvious sustained-release effect as compared with liposome and thermosensitive gel.CONCLUSION Thermo-sensitive diammonium glycyrrhizinate binary liposome gel can reduce drug-release rate and increase its retention time in the rectum.

Preparation of colon-targeted pellets of Prunellae Spica effective components and the in vitro drug-release behaviors / 中成药

AIM To prepare colon-targeted pellets of Prunellae Spica effective components and to evaluate the in vitro drug-release behaviors.METHODS Fluidized bed coating method was adopted in the preparation of pellets.With in vitro accumulative release rate as an evaluation index,hydroxypropyl methyl cellulose (HMPC),polyacrylic resin (Eudragit S100) and triethyl citrate (TEC) amounts as influencing factors,orthogonal test was applied to optimizing the formulation.The in vitro drug-release behaviors were evaluated with rosmarinic acid content as an index.RESULTS The optimal formulation was determined to be 5％ for HPMC amount,70％ for Eudragit S100 amount,and 20％ for TEC amount.The obtained pellets attained an accumulative release rate of more than 90％ in pH 7.6 PBS (transportation for 2 h),while no drug dissolution was found in pH 1.0 HCl (transportation for 2 h) or pH 6.8 PBS (transportation for 3 h).CONCLUSION Colon-targeted pellets of Prunellae Spica effective components can achieve in vitro colon-targeted effect.

Preparation of Compound Anisodamine and Neostigmine Sustained-release Tablet and Study on the in vitro Drug Release Behavior / 中国药房

OBJECTIVE:To prepare the Compound anisodamine and neostigmine sustained-release tablet and study the in vitro drug release behavior. METHODS:Using raceanisodamine and neostigmine methyl sulfate as main medicines,hydroxypropyl meth-yl cellulose as sustained release skeleton material,magnesium stearate as the lubricant,polyvinyl pyrrolidone as the adhesive,pre-gelatinized starch as the thinner,microcrystalline cellulose as the disintegrant and filler,Compound anisodamine and neostigmine sustained-release tablet was prepared by wet granulation method and direct compression method. The in vitro cumulative release rate within 12 h of the 2 main medicines was detected by HPLC method. RESULTS:Compound anisodamine and neostigmine sus-tained-release tablet was successfully prepared,and the in vitro release was basically completed within 12 h,with accumulative re-lease rate of 91.3% for anisodamine and 96.5% for neostigmine. CONCLUSIONS:Compound anisodamine and neostigmine sus-tained-release tablet that can cumulatively release for 12 h is successfully prepared.

Study on Preparation Technology and in vitro Drug Release Behavior of Baicalin Monolithic Osmotic Pump Tablets / 中国药房

OBJECTIVE:To prepare Baicalin monolithic osmotic pump tablets and investigate its in vitro drug release behavior. METHODS:Using accumulative release rate as evaluation index,baicalin solid dispersion was prepared to improve solubility,sin-gle factor test and orthogonal test were used to optimize preparation technology(the amount of penetrating agent and pore-forming agent,weight gaining of coating film) of monolithic osmotic pump tablets using baicalin solid dispersion as intermediate. Release rate and mechanism of samples prepared by optimized technology were investigated in 3 kinds of release medium (water,0.1 mol/L HCl,simulated gastric fluid). RESULTS:The optimal preparation technology was that penetrating agent sodium chloride was 30 mg;pore-forming agent polyethylene glycol 400 was 20% amount of excipient cellulose acetate;weight gaining of coating film was 2%. RSD of 12 h accumulative release rate was 1.06%(n=3)for 3 batches of Baicalin monolithic osmotic pump tablets pre-pared by optimized technology. 12 h accumulative release rate of them in 3 kinds of medium were similar to each other,being all more than 80%. Release equation was in line with zero-order drug release model (r=0.9985). CONCLUSIONS:Prepared Ba-icalin monolithic osmotic pump tablets after optimization can release drug at controlled rate.

Formulation Screening of 5-fluorouracil Polylactic Acid Sustained-release Tablet and Study on Its in vitro Drug-release Mechanism / 中国药房

OBJECTIVE:To screen the formulation of 5-fluorouracil (5-FU) polylactic acid (PLA) sustained-release discs (5-FU-PLA-DS),and study its in vitro drug-release mechanism. METHODS:UV spectrophotometry was used to determine the 5-FU content in the release medium. Using simulate body fluid as release medium,in vitro drug-release test was conducted under 37℃water bath. Using PLA with molecular weight of 3000,6000,10000,15000,20000,15 species of round 5-FU-PLA-DS with drug containing of 1.5,2.5,3.0 mg/piece and 3.0 mm in diameter and 1.0 mm in thickness were prepared. Using effective con-centration sustained release time and cumulative release rate as indexes, the optimal formulation was screened. The form of 5-FU-PLA-DS was observed by scanning electron microscopy after release,and its release mechanism was evaluated. RESULTS:In the optimal formulation, the PLA molecular weight was 20000 and drug containing was 3.0 mg/piece. The prepared 5-FU-PLA-DS can release for 119 d,with cumulative release degree of 100.63% and effective concentration sustained for 91 d. Scanning electron microscopy showed that the microspheres at the surface were degraded to the release medium first,and then the microspheres of inner layer exposed and release drug gradually after PLA degraded. The main mechanism of drug-release was melt-ing and diffusion. CONCLUSIONS:5-FU-PLA-DS is successfully prepared,with long release time in effective concentration,can be degraded step by step from outside to inside and achieve non-synchronous drug-release of microspheres at different layers.

Optimization of Formulation Technology of the Ibuprofen Sustained-release Dropping Pill and Evaluation of Its in vitro Drug-release Behavior / 中国药房

OBJECTIVE:To optimize the formulation technology of Ibuprofen sustained-release dropping pill and evaluate its in vitro drug-release characteristics. METHODS:Using stearic acid as sustained-release matrix,polyethylene glycol 6000 as imme-diate-release matrix,melting method was used to prepare the Ibuprofen sustained-release dropping pill. Using the comprehensive scores of roundness,weight difference,drug loading rate,in vitro drug-release time as indexes,drug-matrix mass ratio,liquid tem-perature,condensation temperature,dropping distance as factors,orthogonal test was adopted to optimize the formulation technolo-gy,and verification test was conducted. In media of deionized water,hydrochloric acid solution (pH 1.2),phosphate buffer (pH 4.5,6.8),the in vitro drug-release were compared between self-made sustained-release dropping pill and commercially available Ibuprofen sustained-release capsule,which were fitted for former drug-release behavior. RESULTS:The optimal formulation tech-nology was as follows as mass ratio of ibuprofen-polyethylene glycol 6000-stearic acid of 4.0:15.3:0.7,liquid temperature of 83 ℃,condensation temperature of 8 ℃,and dropping distance of 11 cm. The weight difference of prepared 3 batches of Ibupro-fen sustained-release dropping pill was 2.067%(RSD=1.19%),roundness was 96.73%(RSD=0.28%),drug loading rate was 96.31%(RSD=0.19%),cumulative release rate in 12 h was 93.05%(RSD=0.81%). The f2 values of self-made sustained-re-lease dropping pill and commercially available Ibuprofen sustained-release capsule were greater than 50,the former one fitted more into Higucci equation(r=0.9881-0.9972). CONCLUSIONS:The formulation technology of Ibuprofen sustained-release dropping pill is successfully optimized,and in vitro drug-release behavior of prepared sustained-release dropping pill is similar to commercial-ly available Ibuprofen sustained-release capsule.

Formulation Screening of 5-fluorouracil Polylactic Acid Sustained-release Tablet and Study on Its in vitro Drug-release Mechanism / 中国药房

OBJECTIVE:To screen the formulation of 5-fluorouracil (5-FU) polylactic acid (PLA) sustained-release discs (5-FU-PLA-DS),and study its in vitro drug-release mechanism. METHODS:UV spectrophotometry was used to determine the 5-FU content in the release medium. Using simulate body fluid as release medium,in vitro drug-release test was conducted under 37℃water bath. Using PLA with molecular weight of 3000,6000,10000,15000,20000,15 species of round 5-FU-PLA-DS with drug containing of 1.5,2.5,3.0 mg/piece and 3.0 mm in diameter and 1.0 mm in thickness were prepared. Using effective con-centration sustained release time and cumulative release rate as indexes, the optimal formulation was screened. The form of 5-FU-PLA-DS was observed by scanning electron microscopy after release,and its release mechanism was evaluated. RESULTS:In the optimal formulation, the PLA molecular weight was 20000 and drug containing was 3.0 mg/piece. The prepared 5-FU-PLA-DS can release for 119 d,with cumulative release degree of 100.63% and effective concentration sustained for 91 d. Scanning electron microscopy showed that the microspheres at the surface were degraded to the release medium first,and then the microspheres of inner layer exposed and release drug gradually after PLA degraded. The main mechanism of drug-release was melt-ing and diffusion. CONCLUSIONS:5-FU-PLA-DS is successfully prepared,with long release time in effective concentration,can be degraded step by step from outside to inside and achieve non-synchronous drug-release of microspheres at different layers.

Optimization of Formulation Technology of the Ibuprofen Sustained-release Dropping Pill and Evaluation of Its in vitro Drug-release Behavior / 中国药房

OBJECTIVE:To optimize the formulation technology of Ibuprofen sustained-release dropping pill and evaluate its in vitro drug-release characteristics. METHODS:Using stearic acid as sustained-release matrix,polyethylene glycol 6000 as imme-diate-release matrix,melting method was used to prepare the Ibuprofen sustained-release dropping pill. Using the comprehensive scores of roundness,weight difference,drug loading rate,in vitro drug-release time as indexes,drug-matrix mass ratio,liquid tem-perature,condensation temperature,dropping distance as factors,orthogonal test was adopted to optimize the formulation technolo-gy,and verification test was conducted. In media of deionized water,hydrochloric acid solution (pH 1.2),phosphate buffer (pH 4.5,6.8),the in vitro drug-release were compared between self-made sustained-release dropping pill and commercially available Ibuprofen sustained-release capsule,which were fitted for former drug-release behavior. RESULTS:The optimal formulation tech-nology was as follows as mass ratio of ibuprofen-polyethylene glycol 6000-stearic acid of 4.0:15.3:0.7,liquid temperature of 83 ℃,condensation temperature of 8 ℃,and dropping distance of 11 cm. The weight difference of prepared 3 batches of Ibupro-fen sustained-release dropping pill was 2.067%(RSD=1.19%),roundness was 96.73%(RSD=0.28%),drug loading rate was 96.31%(RSD=0.19%),cumulative release rate in 12 h was 93.05%(RSD=0.81%). The f2 values of self-made sustained-re-lease dropping pill and commercially available Ibuprofen sustained-release capsule were greater than 50,the former one fitted more into Higucci equation(r=0.9881-0.9972). CONCLUSIONS:The formulation technology of Ibuprofen sustained-release dropping pill is successfully optimized,and in vitro drug-release behavior of prepared sustained-release dropping pill is similar to commercial-ly available Ibuprofen sustained-release capsule.

Preparation and in vitro Drug Release of Daptomycin Liposomes / 中国药师

Objective: To prepare daptomycin liposomes and investigate the in vitro drug release.Methods: Daptomycin liposomes were prepared by an active loading method.The distribution of particle size and zeta potential of liposomes were determined by a laser particle size analyzer.The encapsulation efficiency and in vitro drug release were determined by HPLC.Results: The particle size of daptomycin liposomes was 109.5 nm, the heterogeneous dispersion coefficient was 0.042 and the zeta potential was-6.48 mV.The entrapment efficiency determined by gel column and centrifugation was 50.8% and 50.3%, respectively.The result of in vitro drug release showed that daptomycin liposomes had a good sustained-release effect when compared with daptomycin for injection.Conclusion: Daptomycin liposomes have uniform particle size, which can release drug slowly to reduce administration frequency.

Preparation of gastrodin starch microsphere and its nasal mucoadhesion and in vitro release characteristics / 中草药

Objective: To determine the prescription technology of gastrodin starch microsphere and investigate its nasal mucoadhesion and in vitro release characteristics. Methods: Gastrodin starch microspheres were prepared by compound emulsion crosslinking method. According to the particle diameter, drug loading efficiency (DLE), and entrapment efficiency (EE), the best prescription technology was selected by using single-factor investigation and uniform design. Using toad palate mucosa as model and average residence time as indicator, mucoadhesion of gastrodin starch microsphere was evaluated. Using gastrodin API as a control, paddle method was applied to in vitro release test of gastrodin starch microspheres. The content of gastrodin was determined to calculate the cumulative release percentage. In addition, the curve of drug release in vitro was fitted with different release model to analyze the in vitro release characteristics of gastrodin starch microsphere in nasal cavity, synthetically. Results: The optimum prescription and preparation technology of gastrodin starch microsphere were as follows: gastrodin 2.0 g, starch 4.5 g, liquid paraffin 100.0 mL, Span80 3.5 g, ECH 5.1 mL, preparation temperature 40℃, and rotational speed 1000 r/min. The particle diameter of gastrodin starch microsphere was (47.69±1.92) μm, the DLE and EE of microsphere were (9.78±0.70)% and (35.72±3.28)%, respectively. It was about (176.92±23.25) s that in adhesive powder resided in nasal cavity, which translated into human nasal residence time was just 20-30 min, while the average residence time of gastrodin starch microspheres was extended to (944.33±68.29) s, translated into human nasal residence time was about 3 h. The cumulated release percent of gastrodin starch microspheres was more than 90% in 3 h. Compared with other in vitro release models, Weibull model was the fittest model to gastrodin starch microspheres, the t50 of gastrodin starch microspheres was 40.08 min, and t90 was 245.73 min. Conclusion: Gastrodin starch microspheres prepared with optimum prescription technology have uniform particle diameter, high DLE and EE. Microspheres have good mucoadhesion and sustained release, ensure that gastrodin release gently and completely during the nasal retention period.

Preparation and characterization of epigallocatechin-3-gallate chitosan nanoparticles / 中草药

Objective: To prepare the epigallocatechin-3-gallate (EGCG) chitosan nanoparticles (CS-NPs) and investigate their physicochemical properties. Methods: The EGCG-CS-NPs were prepared by ion gelation method. The formulation variables were optimized by Box-Behnken Design (BBD) of response surface methodology (RSM) of CS concentration (X1), sodium tripolyphosphate concentration (X2), and EGCG concentration (X3) as independent variables and encapsulation efficiency (Y1,%) and particle size (Y2, nm) as dependent variables. The optimized CS-NPs were characterized for encapsulation efficiency (EE), particle size, Zeta potential, morphology, and in vitro drug release behavior of EGCG-CS-NPs were studied. Results: An optimal EGCG-CS-NPs consisting of CS concentration as 2.6 g/L, sodium tripolyphosphate concentration as 1.5 g/L and EGCG concentration as 2.7 g/L. For EE, particle size, Zeta potential of EGCG-CS-NPs were found to be (85.8±3.1)%, (102.2±27.1) nm, and (25.5±4.1) mV, respectively. The CS-NPs were found to be small and spherical as seen in transmission electron microscopy (TEM). The in vitro release data proved that the drug release was steady within 24 h (pH 4.5 PBS). Conclusion: Through optimizing the formulation, we obtain the uniform EGCG-CS-NPs with in vitro sustained-release behavior. This work is useful for the further research on pharmacodynamics of EGCG-CS-NPs.

Characterization and in vitro release of Periplaneta americana-loaded nanoparticles / 中草药

Objective: To prepare Periplaneta americana extract CII-3-loaded nanoparticles for oral administration, and to investigate the in vitro release profile of CII-3-loaded nanoparticles and the protection of nanoparticles for CII-3 extract in vitro. Methods: The in vitro release behavior of the CII-3-loaded nanoparticles was carried out in the artificial gastric juice, artificial intestinal juice, and pH 7.4 PBS, and the fitting of different models was performed based on the accumulative drug release percentages observed by Folin-reagent method; The amino acid content of CII-3 and CII-3-loaded nanoparticles at different time points in artificial gastric juice was determinated by ninhydrin colorimetry and degradation rates of the two drugs were compared. Results: The mean size of the resulted nanoparticles was about (109.9 ± 0.6) nm and the Zeta potential was (-37.5 ± 3.5) mV; The accumulative release level of CII-3-loaded nanoparticles Qt was (22.63 ± 1.17)% in the artificial gastric juice in the first 2 h, and then, in the artificial intestinal juice, the accumulative release level of CII-3-loaded nanoparticles over a period of 60 h was (72.35 ± 1.90)%, which was in line with Higuchi model release equations, Qt = 8.287 2 t1/2 + 7.758 6. The accumulative release level of CII-3-loaded nanoparticles was (72.67 ± 1.65)% over a period of 10 d, which was in line with Weibull equation, lnln[1/(1-Qt)] = 0.403 7 ln(t-0.411 9)-1.713 3; The CII-3 was completely degraded in 4 h in the artificial gastric juice, while about 70% of CII-3 contained in nanoparticles was degraded. Conclusion: CII-3-loaded nanoparticles have a satisfactory sustained in vitro release effect, and the stability of CII-3 contained in the nanoparticles is improved in the artificial gastric juice.

Preparation and in vitro Drug Release of Loxoprofen Sodium Sustained Release Pellets / 中国药师

Objective:To prepare loxoprofen sodium sustained release pellets, and investigate the in vitro drug release behavior. Methods:Loxoprofen sodium loaded pellets were prepared by extrusion-spheronization technology, and the sustained release pellets were prepared with Eudragit RL 30D and Eudragit RS 30D as the sustained release coating film materials. The drug release behavior of loxoprofen sodium sustained release pellets in vitro was studied. Results:Eudragit RL 30D and Eudragit RS 30D with the ratio of 20 ∶80 was used as the sustained release coating film materials, the coating weight was 20%, the plasticizer content was 10%, and the content of talc was 45%. The in vitro release of loxoprofen sodium from the sustained release pellets was steady and entire in 12 h. Conclusion:The release behavior of loxoprofen sodium sustained release pellets is quite satisfactory. And the preparation technology may be used in the industrial production.