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.

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.

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.

Development of composite PLGA microspheres containing exenatide-encapsulated lecithin nanoparticles for sustained drug release

This study aimed to prepare poly(D, L-lactic-co-glycolic acid) microspheres(PLGA-Ms)by a modified solid-in-oil-in-water(S/O/W) multi-emulsion technique in order to achieve sustained release with reduced initial burst and maintain efficient drug concentration for a prolonged period of time. Composite PLGA microspheres containing exenatideencapsulated lecithin nanoparticles(Ex-NPs-PLGA-Ms) were obtained by initial fabrication of exenatide-loaded lecithin nanoparticles(Ex-NPs) via the alcohol injection method,followed by encapsulation of Ex-NPs into PLGA microspheres. Compared to Ms prepared by the conventional water-in-oil-in-water(W/O/W) technique(Ex-PLGA-Ms), Ex-NPs-PLGAMs showed a more uniform particle size distribution, reduced initial burst release, and sustained release for over 60 d in vitro. Cytotoxicity studies showed that Ms prepared by both techniques had superior biocompatibility without causing any detectable cytotoxicity.In pharmacokinetic studies, the effective drug concentration was maintained for over 30 d following a single subcutaneous injection of two types of Ms formulation in rats, potentially prolonging the therapeutic action of Ex. In addition, administration of Ex-NPs-PLGA-Ms resulted in a more smooth plasma concentration-time profile with a higher area under the curve(AUC) compared to that of Ex-PLGA-Ms. Overall, Ex-NPs-PLGA-Ms prepared by the novel S/O/W method could be a promising sustained drug release system with reduced initial burst release and prolonged therapeutic efficacy.

Evaluation of gum mastic(Pistacia lentiscus) as a microencapsulating and matrix forming material for sustained drug release

In this study, a natural gum mastic was evaluated as a microencapsulating and matrixforming material for sustained drug release. Mastic was characterized for its physicochemical properties. Microparticles were prepared by oil-in-oil solvent evaporation method. Matrix tablets were prepared by wet and melt granulation techniques. Diclofenac sodium(DFS) and diltiazem hydrochloride(DLTZ) were used as model drugs. Mastic produced discrete and spherical microspheres with DLTZ and microcapsules with DFS. Particle size and drug loading of microparticles was in the range of 22–62 μm and 50–87%, respectively. Increase in mastic:drug ratio increased microparticle size, improved drug loading and decreased the drug release rate. Microparticles with gum: drug ratio of 2:1 could sustain DLTZ release up to 12 h and released 57% DFS in 12 h. Mastic produced tablets with acceptable pharmacotechnical properties. A 30% w/w of mastic in tablet could sustain DLTZ release for 5 h from wet granulation,and DFS release for 8 h and 11 h from wet and melt granulation, respectively. Results revealed that a natural gum mastic can be used successfully to formulate matrix tablets and microparticles for sustained drug release.

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.

Sustained-release drug delivery systems for the treatment of glaucoma

Glaucoma,a leading cause of irreversible blindness,affects more than 64 million people worldwide and is expected to grow in number due to the aging global population and enhanced methods of detection.Although topical therapies are often effective when used as prescribed,the drawbacks of current medical management methods include poor patient adherence,local and systemic side effects,and in some cases,limited therapeutic efficacy.Novel ocular drug delivery platforms promise to deliver differentiated drug formulations with targeted delivery leveraging patient-independent administration.Several platforms are in various stages of development with promising pre-clinical and clinical data.The Bimatoprost Sustained Release (SR) intracameral implant was approved in the United States in March of 2020,making it the first long-term injectable therapy available for the treatment of glaucoma.This review aims to provide an update on novel sustained release drug delivery systems that are available today as well as those that might be commercialized in coming years.

Novel Gelatin-Adriamycin Sustained Drug Release System for Intravesical Therapy of Bladder Cancer

To reduce recurrence in the patients with bladder cancer after tumor removal through open surgery or transurethral resection, a form of gelatin adriamycin sustained drug release system was developed and its release kinetics both in vitro and in vivo , its efficacy in inhibiting BIU 87 bladder tumor cell growth in vitro and its safety in vivo were studied. The results showed that this system controlled adriamycin release over a period of 21 days in vitro and significantly inhibited BIU 87 cell growth. When this system was injected into rabbit bladder, it sustained adriamycin release for 12 days and the released drug could diffuse 1 cm around the injection point. No major complications were observed except minor acute nonspecific cystitis that could be tolerated well by the animals. This study suggests the possibility of applying this system locally in treating bladder cancer..

Polymeric Hydrogel Nanocapsules: A Thermo and pH Dual-responsive Carrier for Sustained Drug Release

Hydrogel capsules show attractive prospects in drug delivery recently because of high drug loading and sustained release behavior. In this study we reported a simple and convenient route to fabricate poly(acrylic acid)-poly(N-isopropylacrylamide)(PAA-PNIPAm) hydrogel capsules by using hydroxypropylcellulose-poly(acrylic acid)(HPC-PAA) complexes as the templates. The capsules showed a high drug loading(～280% to the weight of capsules) for Doxorubicin hydrochloride. The release of drug from the capsules was responsive to the temperature and p H of the surroundings, showing a low-rate but sustained release behavior favorable for low-toxic and long-term therapy. Together with the convenient preparation, high drug loading, dual responsivity as well as the sustained release feature, it is implied that this polymeric hydrogel capsule might be a promising candidate for new drug carriers.

Preparation and <i>in Vitro</i>Drug Release Evaluation of Once-Daily Metformin Hydrochloride Sustained-Release Tablets

The objective of this study was to develop once-daily metformin hydrochloride sustained-release tablets (MHSRT) and evaluate their in vitro release behavior. MHSRT were prepared by the film coating method. The in vitro drug release rate of MHSRT and the commercial tablets Fortamet? made in the United States of America in water was fitted with zero order kinetic equation, and Ritger-Peppas kinetic equation in 0.1 M HCl and pH 6.8-phosphate buffer, respectively. The similarity factor f2 values of MHSRT in three different dissolution medium were 82, 80 and 74, respectively in comparison with imported Fortamet?, which were all greater than 50. The results of storage-stability showed that MHSRT were stable for at least 6 months under stress condition (40℃ ± 2℃, RH 75% ± 5%). Therefore, in this study, MHSRT were successfully prepared using optimized formulation technologies that meet mass produce. The in vitro release behavior of MHSRT was almost similar to that of imported Fortamet?.

Preparation for Polyvinyl Alcohol Hollow Microsphere and Its Sustained Release Effect on Urea

[Objective] The aim of this study was to discuss the optimizing preparation conditions of polyvinyl alcohol(PVA)hollow microsphere and its application in the production of slow-release urea fertilizer.[Method]PVA hollow microsphere was prepared by the emulsion chemical cross-linking method,while its composition,morphology and particle size was analyzed by technologies of FT-IR,SEM and TEM respectively.Thus,factors such as rate of emulsified speed,crosslink temperature and linking agent amount with effects on morphology and particle size of hollow microsphere were also discussed in this study.Furthermore,based on the optimizing preparation conditions,PVA fertilizer carrier microsphere was prepared by coating urea to investigate its sustained release effect on urea.[Result]The optimizing preparation conditions of polyvinyl alcohol(PVA)hollow microsphere were as follows:rate of emulsified speed 6 000 r/min,crosslink temperature 35 ℃ and linking agent amount 25 ml.PVA fertilizer carrier microsphere had significant sustained release effect on urea,and the optimal cross-linking time was 3 hours.[Conclusion]This study provides theoretical basis for the development of new slow-release fertilizer.

Preparation and Pharmacokinetic Characterization of Sustained Release Melatonin Tablet

Aim To prepare the sustained release melatonin tablet with HPMC matrix and study its pharmacokinetics and bioavailatility. Methods HPMC was used as matrix to formulate the sustained release tablet. The influences of the size of melatonin, type and amount of HPMC, drug loading, type and amount of additives, and compressing pressure were investigated. Plasma concentration of melatonin in dogs after intravenous injection of two doses and oral administration of sustained release tablets and unmodified release capsules was detected by HPLC using fluorescence detector. Results The drug release from sustained release tablets was influenced by the size of melatonin, type and amount of HPMC, drug loading, and type and amount of additives. Melatonin was found to fit two compartment model after intravenous injection, AUC was proportional to doses, and t(1/2β) of two doses has no significant difference. Relative bioavailability of melatonin sustained release tablet to normal capsule was 83.8%, and absolute bioavailability was 3.75% for sustained release tablet and 4.49% for capsule. Conclusion The melatonin sustained release tablet was well formulated. The absolute bioavilability for oral administration of either sustained release tablet or unmodified release capsule of melatonin was less than 5%. The bioavailability of melatonin sustained release tablet was lower than that of unmodified release capsule, but MRT of sustained release tablet was significantly longer than that of capsule.

Study of Sustained Release Phenylpropanolamine Hydrochloride Hydrophilic Matrix Tablets Containing Hydroxypropylmethylcellulose K100M and Carbopol 971P

选用HPMC K100M和卡波普971P为骨架材料，粉末直接压片法制备骨架片，考察释放度，反相高效液相色谱法检测盐酸苯丙醇胺（PPA·HCl）的浓度。释药曲线均符合Higuchi方程（R＞0．98，P＜0．01）。运用正交设计法，以美国市场的PPA·HCl缓释片Acutrim^R为对照，相似因子f2值为指标，筛选获得了最优处方。其工艺重现性合格。研制片在0．1mol·L^-1 HCl,H2O(pH6.5)，磷酸盐缓冲液（PBS）pH5.0,6.8和7.4的介质中，以及在0.1mol·L^-1HCl中释放2h，转移至PBS6．8中释放10h，相对于对照品的f2值为63－74，表明在各介质中两制剂的释药曲线相似。释药影响因素的考察结果表明：在本实验考察的范围内，骨架片在水中的释药速率与HPMC K100M和卡波普971P的用量呈负相关。HPMC K100M和卡波普971P的比例（保持聚合物总用量相同），硬脂酸镁量和骨架片硬度对释药速率无显著性影响。

Controlled release of dexamethasone from fibrin sealant for intratympanic administration in inner ear therapy

The aim of the present work was to show the sustainability of fibrin sealant in releasing dexamethasone and adjust the protocol for clinical application of the novel method in the treatment of Meniere’s disease (MD) and sudden sensorineural hearing loss (SSHL).Gelation occurred shortly after mixing dexamethasone-containing fibrinogen with thrombin.Dexamethasone was constantly released for at least 16 d at a stable level after 7d in protocol 1 (low-dose),while it was robustly released within 4 d and slowed afterward until 10 d in protocol 2(high-dose).There were significant differences among the time points in Protocol 2 (p<0.01,ANOVA),and the exponential model with the formula y=15.299*e~(-0.483*t) fits the association.The estimated concentration of dexamethasone released on 7 d in protocol 2 was slightly lower than that observed in protocol 1.The fibrin sealant is capable of constantly releasing dexamethasone with adjustable dynamics.Targeted and minimally invasive administration of the material can be achieved in the clinic by sequential injections of the fluids using a soft-tipped catheter.

Pharmacokinetics of Moclobemide Sustained Release Tablets after Multiple Oral Dose Administration in Healthy Volunteers

To investigate the pharmacokinetic characteristics of moclobemide sustainedrelease tablets after multiple oral dose administration in healthy Chinese volunteers. MethodsMoclobemide sustained release tablets were given as a multiple oral dose regimen of 300 mg oncedaily for five consecutive days to 12 healthy volunteers. The concentrations of moclobemide inplasma were determined by reversed-phase high performance liquid chromatography. The partialpharmacokinetic parameters were calculated using 3p97 pharmacokinetic program. Results Theconcentration-time profile fitted an one-compartment model best. The steady-state pharmacokineticparameters of moclobemide sustained release tablets after multiple oral doses were as follows:C_(max) was (1 950 +- 156) μg· L^(-1), T_(max) was (6.00 +-1.55) h, T_(1/2(kel)) was (3.14 +-0.12)h, AUC_(ss 0-24) was (22 836 +- 1 842) μg·h· L^(-1), MRT was (7.68+-0.36) h, CL/F_((s)) was(20.2+-2.1) L·h^(-1), and V/F_((c)) was (91.4+-9.4) L, respectively. No marked adverse events werenoted during this study. Conclusion The formulation has a sustained-release effect and goodtolerance in the healthy volunteers, which provides useful information for clinical practice.

A matrix metalloproteinase-responsive hydrogel system controls angiogenic peptide release for repair of cerebral ischemia/reperfusion injury

Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.

Influence of Preparation Factors on the Sustained Release of Nifedipine from Eudragit RL/RS Microspheres

Sustained release Eudragit RL/RS microspheres encapsulating nifedipine were prepared using the acetone/liquid paraffin emulsion solvent evaporation method. The influence of different preparation factors on release of the drug in vitro was investigated. The release rate of nifedipine from the microspheres increased with increasing Eudragit RL/RS ratio and stirring rate during the preparation, and with decreasing the polymer concentration of internal phase and microsphere size. It was found that a linear relationship existed between the microsphere size and the time of 50% drug release. The drug release rate increased with increasing nifedipine content from 4.2 to 16.7% and was more rapid than the dissolution rate of pure nifedipine particles. However, the release rate of the microspheres with 26.6% drug content decreased significantly and was slower than the dissolution rate of pure drug particles. This was attributed mainly to the nifedipine dispersion state in the microspheres as confirmed by the differential thermal analysis and X ray diffraction study, which showed that nifedipine was present in an amorphous or molecular state in the microspheres with 4.2, 9.4 and 16.7% drug, whereas partly in the crystalline state in the microspheres with 26.6% drug. The amounts released for less than 70% nifedipine can be fitted to Higuchi square root of time model, independent of polymer ratio, drug content and microsphere size.

Preparation and Drug-Release Property of Polycaprolactone (PCL)/Polyglycolic Acid (PGA) Composite Masterbatch with Drug of Tea Polyphenols (TPs)

In order to effectively control the drug-release rate of medical textiles,biodegradable polycaprolactone(PCL) and polyglycolic acid(PGA) were blended at various mass ratios to prepare composite masterbatches for medical textiles.The surface morphology and the chemical structure of the masterbatches were analyzed.The crystallization,mass losses,strengths and drug-release rates of the composite masterbatches at different PCL/PGA mass ratios were explored.The results show that the degradation rate of the PGA carrier is obvious higher than that of the PCL carrier,and PCL,PGA and the tea polyphenol(TP) drug just physically mix without chemical reaction.During the degradation,the strength of the composite masterbatches gradually decreases.In addition,the drug-release rates of composite masterbatches at different mass ratios are different,and the more the PGA in the composite masterbatches,the faster the drug release of the composite masterbatches.The drug-release rate of the composite masterbatches can be controlled by adjusting the contents of PCL and PGA.

Anorectal Pharmacodynamics and In Vitro Drug Release of Clerodendrum bungei Steud.Extract Gel

[Objectives]To determine the optimal preparation technology of Clerodendrum bungei Steud.extract gel by orthogonal test and gel quality test method in General Rule 0114 of Chinese Pharmacopoeia(Volume IV,2020 Edition),and to study its anorectal pharmacodynamics and drug release in vitro.[Methods]Carbomer 940,propylene glycol and absolute ethyl alcohol were selected as the main factors,and the preparation technology of C.bungei Steud.extract gel was optimized by orthogonal test.The mouse model of ulcerative hemorrhoids was established with glacial acetic acid(HAC)and compared with Ma Yinglong musk hemorrhoids ointment.The recovery of trauma was compared between the two groups.At the same time,porcine small intestine was used as semi-permeable membrane to make diffusion cell to simulate anal environment,and the drug release in vitro was studied.[Results]The C.bungei Steud.extract gel was smooth in appearance and good in stability.It could effectively treat anal ulcer in mice and release quickly in vitro.[Conclusions]The formula is reasonable,and the effect of animal experiment is remarkable,which can provide a new treatment plan for ulcerative hemorrhoids.

Preparation and in vitro Release Performance of Sustained-release Captopril/Chitosan-gelatin Net-polymer Microspheres

The captopril/Chitosan-gelatin net-polymer microspheres(CTP/CGNPMs) were prepared using Chitosan(CTS) and gelatin(GT) by the methods of emulsification,cross-linked reagent alone or in combination and microcrystalline cellulose(MCC) added in the process of preparation of microspheres,which aimed to eliminate dose dumping and burst phenomenon of microspheres for the improvement of the therapeutic efficiency and the decrease of the side effects of captopril(CTP). The results indicated that CTP/CGNPMs had a spherical shape,smooth surface and integral structure inside but no adhesive phenomena in the preparation. The size distribution ranged from 220 μm to 280 μm. The CTP release test in vitro demonstrated that CTP/CGNPMs played the role of retarding the release of CTP compared with ordinary CTP tablets. The release behaviors of CGNPMS were influenced by preparation conditions such as experimental material ratio(EMR) and composition of cross linking reagents. Among these factors,the EMR(1/4),CLR(FA+SPP) and 0.75% microcrystalline cellulose(MCC) added to the microspheres constituted the optimal scheme for the preparation of CTP/CGNPMs. The ER,DL and SR of CTP/CGNPMs prepared according to the optimal scheme were 46.23±4.51%,9.95±0.77% and 261±42%,respectively. The CTP/CGNPMs had the good characteristics of sustained release of drug and the process of emulsification and cross-linking were simple and stable. The CGNPMs are likely to be an ideal sustained release formulation for water-soluble drugs.