Coating Process of Paeonol Sustained Release Pills

[Objectives] To study the coating process of paeonol sustained release pills by extrusion-spheronization method taking ethyl cellulose as the coating material. [Methods] Paeonol pills were made by Auari AW-95 Full Automatic Pill Making Machine. Coating of paeonol sustained release pills was prepared by Auari Mini Pill Polishing Machine. The prescription and process factors of paeonol sustained release pills coating were investigated by single factor experiment and orthogonal experiment. The release of paeonol sustained release pills was determined according to the cumulative release curve of paeonol. [Results] The prepared paeonol sustained release pills released slowly within 24 h, and the release rate reached 80% in 12 h. [Conclusions] The prepared paeonol sustained release pills basically meet the 24 h sustained release standard, and can be further developed and applied.

Sustained release donepezil loaded PLGA microspheres for injection:Preparation,in vitro and in vivo study

The purpose of this study was to develop a PLGA microspheres-based donepezil(DP)formulation which was expected to sustain release of DP for one week with high encapsulation efficiency(EE).DP derived from donepezil hydrochloride was encapsulated in PLGA microspheres by the O/W emulsion-solvent evaporation method.The optimized formulation which avoided the crushing of microspheres during the preparation process was characterized in terms of particle size,morphology,drug loading and EE,physical state of DP in the matrix and in vitro and in vivo release behavior.DP microspheres were prepared successfully with average diameter of 30m,drug loading of 15.92±0.31%and EE up to 78.79±2.56%.Scanning electron microscope image showed it has integrated spherical shape with no drug crystal and porous on its surface.Differential scanning calorimetry and X-ray diffraction results suggested DP was in amorphous state or molecularly dispersed in microspheres.The Tg of PLGA was increased with the addition of DP.The release profile in vitro was characterized with slow but continuous release that lasted for about one week and fitted well with first-order model,which suggested the diffusion governing release mechanism.After single-dose administration of DP microspheres via subcutaneous injection in rats,the plasma concentration of DP reached peak concentration at 0.50 d,and then declined gradually,but was still detectable at 15 d.A good correlation between in vitro and in vivo data was obtained.The results suggest the potential use of DP microspheres for treatment of Alzheimer’s disease over long periods.

Preparation and Characterization of Potassium Monopersulfate/Ethyl Cellulose Microcapsules and Their Sustained Release Performance

Environmental cleaning is an important aspect of bacteria control.Ethyl cellulose microcapsules containing potassium monopersulfate(PMCM)were prepared by emulsified solvent diffusion method.The chemical structure and microstructure of the obtained PMCM was characterized by methods of Fourier transform infrared spectroscopy(FT-IR),optical microscopy,scanning electron microscopy and X-ACT energy dispersive X-ray spectroscopy.The SEM micrographs of the PMCM containing 21.6%of C,46.8%of O,10.7%of S and 19.4%of K was relatively smooth.Thermal stability,sustained release performance,and antimicrobial activity of PMCM were investigated.The results showed that the drug loading and encapsulation efficiency of PMCM were 30.3%and 42.6%respectively.Potassium monopersulfate was fully released after 8 h,following a Fickian diffusion mechanism.Results showed that the microcapsules prepared with a high concentration of potassium monopersulfate solution showed a good antimicrobial effect.The microcapsule wall of the resulting PMCM increased with increasing ethyl cellulose content and had high thermal stability from the data of 69%residue rate.The excellent thermal stability and high sustained release performance of PMCM showed high application value.

Sustained release of exosomes loaded into polydopamine-modified chitin conduits promotes peripheral nerve regeneration in rats

Exosomes derived from mesenchymal stem cells are of therapeutic interest because of their important role in intracellular communication and biological regulation.On the basis of previously studied nerve conduits,we designed a polydopamine-modified chitin conduit loaded with mesenchymal stem cell-derived exosomes that release the exosomes in a sustained and stable manner.In vitro experiments revealed that rat mesenchymal stem cell-derived exosomes enhanced Schwann cell proliferation and secretion of neurotrophic and growth factors,increased the expression of Jun and Sox2 genes,decreased the expression of Mbp and Krox20 genes in Schwann cells,and reprogrammed Schwann cells to a repair phenotype.Furthermore,mesenchymal stem cell-derived exosomes promoted neurite growth of dorsal root ganglia.The polydopamine-modified chitin conduits loaded with mesenchymal stem cell-derived exosomes were used to bridge 2 mm rat sciatic nerve defects.Sustained release of exosomes greatly accelerated nerve healing and improved nerve function.These findings confirm that sustained release of mesenchymal stem cell-derived exosomes loaded into polydopamine-modified chitin conduits promotes the functional recovery of injured peripheral nerves.

Characterization of physiochemical and biological properties of spherical protein crystals for sustained release

This study presents an exploration on extending the action of therapeutic proteins by crystallization strategy without new molecular entities generation.Recombinant human interferon a-2b(rhIFN),a model protein drug in this case,was crystallized using a hanging drop vapor diffusion method.A novel chelating technique with metal ions was employed to promote crystals formation.The physico-chemical characterization of the protein crystals,including morphology,particle size,X-ray diffraction,circular dichroism and biological potency evaluations were performed.In addition,the in vitro release behavior of rhIFN from crystal lattice suggested an exciting possibility of protein crystals as a longacting formulation.The work described here demonstrates the possibility of spherical crystals of biomacromolecules for controllable delivery application of therapeutic proteins.

Polymeric microneedle-mediated sustained release systems: Design strategies and promising applications for drug delivery

Parenteral sustained release drug formulations, acting as preferable platforms for longterm exposure therapy, have been wildly used in clinical practice. However, most of these delivery systems must be given by hypodermic injection. Therefore, issues including needle-phobic, needle-stick injuries and inappropriate reuse of needles would hamper the further applications of these delivery platforms. Microneedles (MNs) as a potential alternative system for hypodermic needles can benefit from minimally invasive and self-administration. Recently, polymeric microneedle-mediated sustained release systems (MN@SRS) have opened up a new way for treatment of many diseases. Here, we reviewed the recent researches in MN@SRS for transdermal delivery, and summed up its typical design strategies and applications in various diseases therapy, particularly focusing on the applications in contraception, infection, cancer, diabetes, and subcutaneous disease. An overview of the present clinical translation difficulties and future outlook of MN@SRS was also provided.

Formation of composite hydrogel of carboxymethyl konjac glucomannan/gelatin for sustained release of EGCG

Development of functional bioinspired hydrogels that have good releases control character is necessary for the application of these materials in biomedical engineering.Herein,we report a composite hydrogel prepared from several biocompatible carboxymethyl konjac glucomannan(CKGM)/gelatin(G)/tannic acid(TA)functional nano-hydroxyapatite(TA@n-HA),which has good biodegradability and pH sensitivity.The mechanism of interaction between hydrogels was confirmed by Fourier transform infrared spectroscopy,X-ray diffraction,Scanning electron microscopy and Thermogravimetric analysis.The physico-chemical properties of CKGM/G hydrogels have been significantly improved through the incorporation of TA@n-HA within the matrix.Studies in the sustained release of epigallocatechin gallate(EGCG)demonstrated that the TA@n-HA/CKGM/G hydrogels exhibit not only better pH sensitive properties,but also enhanced biocompatibility and encapsulation in comparison to the matrix devoid of TA@n-HA.Consequently,TA@n-HA/CKGM/G hydrogels using EGCG as a drug release model show the potential for drug delivery.

Efficacy of Metoprolol Succinate Sustained Release Tablets Combined with Wenxin Granules in the Treatment of Coronary Heart Disease Arrhythmia

Objective:To explore the effect of metoprolol succinate sustained-release tablets combined with Wenxin Granules in the treatment of coronary heart disease patients with arrhythmia.Methods:The research objects were 50 patients with arrhythmia who were treated in our hospital from September 2019 to September 2020.According to different treatment methods,they were divided into observation group(Wenxin Granule+metoprolol succinate treatment)and control group(metoprolol succinate treatment),25 cases in each group.The curative effects of the two groups were compared.Results:After treatment,there was no significant difference in rnn50,RMSSD,sdnni and SDANN between the two groups(P>0.05).Compared with the control group,the SDNN in the observation group was higher than that in the control group(P<0.05);Before treatment,there was no significant difference in the above indexes between the two groups(P>0.05);The effective rates of the observation group and the control group were 92.00%and 68.00%respectively,and the curative effect of the observation group was higher than that of the control group(P<0.05);There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion:In the treatment of patients with coronary heart disease and arrhythmia,Wenxin Granule Combined with metoprolol succinate sustained-release tablets has significant effect,which can effectively improve the dynamic electrocardiogram indexes of patients,improve the clinical efficacy,and has high safety.

Enhanced delivery efficiency and sustained release of biopharmaceuticals by complexation-based gel encapsulated coated microneedles:rhIFNα-1b example

Coated microneedles(MNs) are widely used for delivering biopharmaceuticals. In this study, a novel gel encapsulated coated MNs(GEC-MNs) was developed. The water-soluble drug coating was encapsulated with sodium alginate(SA) in situ complexation gel. The manufacturing process of GEC-MNs was optimized for mass production. Compared to the water-soluble coated MNs(72.02% ± 11.49%), the drug delivery efficiency of the optimized GEC-MNs(88.42% ± 6.72%) was steadily increased, and this improvement was investigated through in vitro drug release. The sustained-release of BSA was observed in vitro permeation through the skin. The rhIFN α-1 b GEC-MNs was confirmed to achieve biosafety and 6-month storage stability. Pharmacokinetics of rhIFN α-1 b in GEC-MNs showed a linearly dosedependent relationship. The AUC of rhIFN α-1 b in GEC-MNs(4.51 ng/ml ·h) was bioequivalent to the intradermal(ID) injection(5.36 ng/ml ·h) and significantly higher than water-soluble coated MNs(3.12 ng/ml ·h). The rhIFN α-1 b elimination half-life of GEC-MNs, soluble coated MNs, and ID injection was 18.16, 1.44, and 2.53 h, respectively. The complexation-based GECMNs have proved to be more efficient, stable, and achieve the sustained-release of watersoluble drug in coating MNs, constituting a high value to biopharmaceutical.

A Novel Nerve Guidance Conduit with Sustained Release of NGF Enhances Sciatic Nerve Regeneration

Based on diffusion of nerve growth factor（NGF） from degradable material,a novel nerve guidance conduit（NGC） with sustained NGF release was prepared by embedding NGF into a degradable RGD-modified composite which has good cell affinity and biocompatibility.In vitro,the NGF release was quantified using enzyme-linked immunosorbent assay method,and the bioactivity of released NGF was examined by PC-12 cell bioassay.In vivo,the performance of the NGF-containing conduit was examined using rat sciatic nerve defect model.The experimental results show that the NGF release process is prolonged over 30 days,and at least some degree of NGF bioactivity is preserved after the fabrication process.Due to the promoting effect of bioactive released NGF on nerve regeneration,the performance of NGC for nerve repair is improved significantly.The results of this study indicate that the sustained NGF release system is suitable for peripheral nerve repair.

HPLC Method for the Determination of Tamsulosin Hydrochloride in Sustained Release Tablets

The development and validation of an isocratic high performance liquid chromatographic method is described for the determination of tamsulosin hydrochloride in sustained release tablets. The determination was performed on a Diamonsil BDS C18 column with a mobile phase consisting of a mixture of acetonitrile, methanol and 0 5% phosphoric acid solution (20∶30∶50, V/V/V ) at a flow rate of 1 0 mL/min. UV detection was made at 274 nm. The linear range for tamsulosin hydrochloride was 0 81-8 10 μg/mL. The mean recovery was 99 8% ( S R=0 7%, n =9), and the precision was found to be 0 45% ( n =9). The proposed method can be used for routine analysis of tamsulosin hydrochloride in sustained release tablets.

Bioequivalence of Progesterone Sustained Release Suppository in Rabbits

Summary： To study the bioequivalence of a kind of progesterone sustained release suppository, a randomized cross over study was conducted in 12 rabbits. A single rectal dose of 2.75 mg/kg progesterone sustained released suppository （tested formulation, T） and progesterone suppository （reference formulation, R） was administered; a muhiple dose of 2.75 mg/kg was given up to seven times with an interval of 8 h. Concentrations in serum were determined by a competitive enzyme immunoassay. The main parameters of T were： for single and multiple doses, C was 48.8±11.8 ng/mL and 43.5±9.4 ng/mL. Tmax was 0.5±0.3 h and 0. 4±0.3 h, AUC〈（0-21h） was 362. 4±143 ng·h·mL^-1 and 310.6±70. 3 ng·h·mL^-1 , respectively. The relative bioavailability of T to R were （104.2±13.4） % and （111.4±19. 1） %, respectively. Statistical analysis showed that the two formulations were bioequivalent and T had sustained released feature.

SUSTAINED RELEASE OF LEVONORGESTREL USING POLYPHOSPHATE AS DRUG CARRIER

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Clinical Efficacy of Metoprolol Succinic Acid Sustained Release Tablets Combined with Trimetazidine in the Treatment of Gastrointestinal Tumors with Angina Pectoris

Objective:To investigate the clinical efficacy of metoprolol succinate sustained-release tablets combined with trimetazidine in the treatment of gastrointestinal tumors with angina pectoris.Methods:We enrolled the 58 patients with digestive tract tumor merger angina in November 2017-October 2019 and analysis the hospital clinical data by retrospective method.We included patients with routine treatment in control group(n=31 cases)and the subjects treated with increased dose of succinic acid metoprololzyban joint with trimetazidineinobservation group(n=27 cases)according to the different treatment group.Results:The effective rate of angina pectoris treatment in the observation group was higher than that in the control group.Furthermore,the incidence of adverse reactions was lower than that in the control group and the difference was statistically significant(P<0.05).Conclusion:Metoprolol succinic acid sustained release tablets combined with trimetazidine in the treatment of gastrointestinal tumors with angina pectoris can improve the efficacy of angina pectoris.The drug use is safe and worthy of clinical use.

Construction and properties of venlafaxine hydrochloride sustained release system based on hollow mesoporous silica microspheres

The aim of this work is to develop a venlafaxine hydrochloride sustained release system based on hollow mesoporous silica microspheres(HMSMs).HMSMs were innovatively prepared with tetraethyl silicate(TEOS)as the precursor and volatile n-heptane as a soft template.The obtained HMSMs show a well-defined hollow structure with an average size of 967 nm and pore volume of 0.85 cm^(3)/g,implying it is a potential drug carrier.Subsequently,venlafaxine hydrochloride(VF)was absorbed in the HMSMs with a content of 37.67% or so.The sustained release effect is further measured by the dissolution in-strument at 37℃ and 50 rpm in ultrapure water.The results showed that the HMSMs/VF system shows good sustained release properties compared with sustained release tablets with hydroxypropyl meth-ylcellulose as the main component.This HMSMs sustained release system appears to be a promising candidate for a sustained drug release.

Preparation of multicore millimeter-sized spherical alginate capsules to specifically and sustainedly release fish oil

Specific and sustained release of nutrients from capsules to the gastrointestinal tract has attracted many attentions in the field of food and drug delivery.In this work,we reported a monoaxial dispersion electrospraying-ionotropic gelation technique to prepare multicore millimeter-sized spherical capsules for specific and sustained release of fish oil.The spherical capsules had diameters from 2.05 mm to 0.35 mm with the increased applied voltages.The capsules consisted of uniform(at applied voltages of≤10 k V)or nonuniform(at applied voltages of>10 k V)multicores.The obtained capsules had reasonable loading ratios(9.7%-6.3%)due to the multicore structure.In addition,the obtained capsules had specific and sustained release behaviors of fish oil into the small intestinal phase of in vitro gastrointestinal tract and small intestinal tract models.The simple monoaxial dispersion electrospraying-ionotropic gelatin technique does not involve complicated preparation formulations and polymer modification,which makes the technique has a potential application prospect for the fish oil preparations and the encapsulation of functional active substances in the field of food and drug industries.

Selenized liposomes with ameliorative stability that achieve sustained release of emodin but fail in bioavailability

Stability of liposomes plays a crucial role in drug delivery,especially in oral aspect.The structural modification of liposomes has been the orientation of efforts to improve their stability and enable the controllability of payload release.This study reported a selenylation strategy to optimize the liposomal structure in an attempt to enhance the nanocarrier’s stability,hence the bioavailability of emodin(EM),an active compound with poor water-solubility.EM-loaded selenized liposomes(EM-Se@LPs)were prepared by thin film dispersion followed by in situ reduction technique.The results showed that EM-Se@LPs were provided with enhancive gastrointestinal stability and exhibited sustained release of drug compared with EM-loaded liposomes(EM-LPs).However,the modified liposomes with Se depositing onto the interior and exterior bilayers did not substantially facilitate absorption of EM.The reinforced structure of liposomes irrelevant to absorption was affirmed to be due to good stability and absorbability of EM itself.Nevertheless,the present work provides an alternative option for stabilization of liposomes instead of conventional methods,which may be promising for oral delivery of physiologically unstable and/or poorly absorbed drugs and systemic drug delivery.

Study on Sustained-Release Pesticides Blended with Fosthiazate-Stearic Acid/Expanded Perlite

The low utilization rate of pesticides makes the migration of pesticides in water and soil,which brings great harm to the ecosystem.The development of pesticide carriers with good drug loading capacity and release control abil-ity is an effective method to realize effective utilization of pesticides and reduce pesticide losses.In this work,fosthiazate-stearic acid/expanded perlite sustained-release particles were successfully prepared by vacuum impregnation using expanded perlite(EP)as carrier,fosthiazate(FOS)as model pesticide and stearic acid(SA)as hydrophobic matrix.The structure and morphology of the samples were studied by BET,FT-IR,TGA,XRD,DSC and SEM.The effects of different mass ratios of FOS to SA on loading capacity and release rate at 24 h were investigated.The sustained release behavior of FOS-SA/EP at different temperatures and pH values was investigated by static dialysis bag method.The results showed that FOS and SA were adsorbed in EP pores by physical interaction.With the mass ratios of FOS to SA decreasing from 7:3 to 3:7,the 24 h release rate of FOS-SA/EP decreased from 18.77%to 8.05%,and the drug loading decreased from 461.32 to 130.99 mg/g.FOS-SA/EP showed obvious temperature response at 25℃,30℃ and 35℃,the cumulative release rate(CRR)of 200 h were 33.38%,41.50%and 51.17%,respectively.When pH=5,the CRR of FOS was higher than that of pH=7,and the CRR of FOS for 200 h were 49.01%and 30.12%,respectively.At different temperatures and pH=5,the release mechanism of FOS-SA/EP belongs to the Fickian diffusion mechanism;When pH=7,the diffusion mechanism is dominant,and the dissolution mechanism is complementary.

Preparation and evaluation of sustained-release diltiazem hydrochloride pellets

In this study,diltiazem hydrochloride(DTZ)pellets were prepared successfully by extrusionespheronization method.Then methacrylic acid and ethylcellulose coating formulations were employed to make the DTZ pellets sustained release.The pellets with different coatings were investigated by in vitro dissolution tests.At last,the pellets with the best coating copolymer were subjected to pharmacokinetic studies in beagle dogs.The dissolution profiles of pellets coated with Eudragit
NE30D were similar to Herbesser
,one of the marketed sustained release capsules.In the bioavailability study,the principal pharmacokinetic parameters of self-made pellets and the marketed ones were comparable;the relative bioavailability of DTZ sustained release capsules compared with Herbesser
was 98.5
36.4%.All the data indicated self-made sustained pellets could prolong the release of DTZ,decrease the fluctuation of drug level in vivo,and increase the compliance of patients.