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.

Preparation and Characterization in vitro of Sustained-release Captopril/ Chitosan-gelatin Net-polymer Microspheres(Cap/CGNPMs)

The captopril/ Chitosan-gelatin net-polymer microspheres （ Gap/ CGNPMs ） were prepared using Chitosan （ CS ） and gelatin （ Gel ） by the methods of emulsification. A cross linked reagent alone or in combination with microcrystalline cellulose （ MCC ） was added in the process of preparation of microspheres to eliminate dose dumping and burst phenomenon of microspheres for the improvemeat of the therapeutic efficiency and the decrease of the side effects of captopril （ Cap ）. The results indicate that Cap/ CGNPMs have a spherical shape , smooth surface roorphology and integral inside structure and no adhesive phenomena and good roobility , and the size distribution is mairdy from 220 to 280 μm. Researches on the Cap release test in vitro demonstrate that Cap/ CGNPMs are of the role of retarding release of Cap compared with Cap ordinary tablets （COT）, embedding ratio （ER） , drug loading （ DL ）, and swelling ratio （ SR ）, and release behaviors of CGNPMS are influenced by process conditions of preparation such as experimental material ratio （EMR） , composition of cross linking reagents. Among these factors , the EMR（1/4）, CLR （ FOR ＋ TPP） and 0.75% microcrystulline cellulose （MCC） added to the microspheres are the optimal scheme to the preparation of Cap/CGNPMs. The Cap/CGNPMs have a good characteristic of sustained release of drug, and the process of emulsifieation and crossinking process is simple and stable. The CGNPMs is probable to be one of an ideal sustained release system for water-soluble drugs.

The preparation and the in-vitro pharmacodynamics study of the intracapsular sustained-release preparations for the prevention of posterior capsule opacification

Docetaxel-loaded sustained-release preparation based on 2-Hydroxyethyl methacrylate(HEMA)and Methyl methacrylate(MMA)cross-linked copolymer(P(HEMA-co-MMA))was prepared to examine the potential use for preventing posterior capsule opacification(PCO).The preparations were prepared by polymerizing the mixture of HEMA,MMA,cross-linking agent(EGDMA),initiator(AIBN)and docetaxel.The influence factors and mechanism of drug release were studied in the experiments.FT-IR,X-RD and SEM methods were used to characterize the polymer(P(HEMA-co-MMA))and docetaxel-loaded sustained-release preparations.Biocompatibility of P(HEMA-co-MMA)and in-vitro effect of docetaxel-loaded sustained-release preparations were also evaluated.The results showed that docetaxel could release sustainedly from these preparations prepared by cross-linking polymerization.And the release rate could be accelerated by increasing the MMA ratio or EGDMA ratio of the polymer.Release mechanism of docetaxel fitted the Higuchi model well.The results of IR and X-RD showed that only a hydrogen bond was formed between docetaxel and P(HEMA-co-MMA).Docetaxel dispersed in P(HEMA-co-MMA)in amorphous form.The elution test showed that P(HEMA-co-MMA)had good biocompatibility and the in-vitro pharmacodynamics study proved that docetaxel could release stably from the preparations and inhibit HLECs’proliferation.The docetaxel-loaded sustained-release preparations proved to be a promising therapy for preventing PCO.These results also lay a theoretical and experimental foundation for the future.

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.

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.

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.

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.

Application of D-Optimal Study Design with Contour Surface Response for Designing Sustained Release Gliclazide Matrix Tablets

An optimized formulation of a sustained release tablet of Gliclazide was developed. The use of Doptimal design with a polynomial statistical model to analyze dissolution data reduced the number of laboratory tests required to obtain an optimal dosage form. The final formulation contained 22 mg of Methocel&regE15LV, 16.5 mg Methocel&regE15 and 10.0 mg of Dibasic Calcium Phosphate per 30 mg Gliclazide sustained release tablet. Dissolution studies performed on tablets from 5000 tablet test batches released greater than 90 percent of loaded drug in eight hours. Drug release from the optimized tablets followed a pattern more closely similar to zero-order than other mechanisms of drug release tested. Storage of tablets in accelerated and ambient conditions for 6 and 12 months respectively did not alter any of the physico-chemical properties, drug release or the drug release rate compared to initial observations and dissolution data of the prepared tablets. The addition of potassium phosphate and monosodium phosphate to the tablet reduced the effect pH has on Gliclazide dissolution compared to the commercially available product.

Release performance and sustained-release efficacy of emamectin benzoate-loaded polylactic acid microspheres

High-performance liquid chromatography （HPLC） was employed to determine drug release rates based on emamectin benzoate concentrations in the medium. Release kinetics equations were used to fit the drug release behavior. The effects of particle size and release medium pH on the release rate were also investigated. The indoor toxicity of emamectin benzoate-loaded polylactic acid microspheres on the diamondback moth larva （Plutella xylostella） was studied to explore drug sustained-release performance. In acidic and neutral media, the drug release behavior of the microspheres was in accord with the first-order kinetics equation. Increasing the spray dosage of emamectin benzoate-loaded polylactic acid microspheres initially resulted in an equivalent insecticidal efficacy with the conventional emamectin benzoate microemulsion. However, the drug persistence period was four-fold longer than that observed using the conventional formulation. The developed emamectin benzoate-loaded polylactic acid microspheres showed dramatic sustained-release performance. A treatment threshold of greater than 35 mg mL-1 was established for an efficient accumulated release concentration of emamectin benzoate-loaded microspheres.

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.

Methylprednisolone microsphere sustained-release membrane inhibits scar formation at the site of peripheral nerve lesion

Corticosteroids are widely used for the treatment of acute central nervous system injury. However, their bioactivity is limited by their short half-life. Sustained release of glucocorticoids can prolong their efficacy and inhibit scar formation at the site of nerve injury. In the present study, we wrapped the anastomotic ends of the rat sciatic nerve with a methylprednisolone sustained-release membrane. Compared with methylprednisone alone or methylprednisone microspheres, the methylprednisolone microsphere sustained-release membrane reduced tissue adhesion and inhibited scar tissue formation at the site of anastomosis. It also increased sciatic nerve function index and the thickness of the myelin sheath. Our findings show that the methylprednisolone microsphere sustained-release membrane effectively inhibits scar formation at the site of anastomosis of the peripheral nerve, thereby promoting nerve regeneration.

Tunable and sustained-release characteristics of venlafaxine hydrochloride from chitosan–carbomer matrix tablets based on in situ formed polyelectrolyte complex film coating

The objective of this study is to design sustained-release tablets using matrix technology, which can well control the release of highly water-soluble drugs with good system robustness and simple preparation process. Taking venlafaxine hydrochloride(VH) as a drug model, the feasibility of using chitosan(CS), carbomer(CBM) combination system to achieve this goal was studied. Formulation and process variables influencing drug release from CS–CBM matrix tablets were investigated. It was found that CS–CBM combination system weakened the potential influence of CS, CBM material properties and gastric emptying time on drug release profile. Demonstrated by direct observation, differential scanning calorimetry(DSC) and Fourier transform infrared spectroscopy(FTIR), in situ self-assembled polyelectrolyte complex(PEC) film was formed on the tablet surface during gastrointestinal tract transition, which contributed to the tunable and robust control of drug release. The sustained drug release behavior was further demonstrated in vivo in Beagle dogs, with level A in vitro and in vivo correlation(IVIVC) established successfully. In conclusion, CS–CBM matrix tablets are promising system to tune and control the release of highly water-soluble drugs with good system robustness.

Effect of rhBMP-2 sustained-release nanocapsules on the ectopic osteogenesis process in Sprague-Dawley rats

Objective:To explore the effect of sustained-release recombinant human bone morphogenetic protein-2(rhBMP-2) on ectopic osteogenesis in the muscle pouches of rats through preparing rhBMP-2 sustained-release capsules by wrapping morphogenesis protein bones-2(BMP-2)using chitosan nanoparticles,and compositing collagen materials.Methods:Twenty four SpragueDawley rats were randomly divided into four groups with six rats in each group,that is Group A(control group),Group B(only treated with collagen),Group C(rhBMP-2+collagen treated group) and Group D(rhBMP-2/cs+collagen treated group).The composite materials for each group were implanted in the bilateral peroneal muscle pouches in rats.The peroneal muscles were only separated without implanting any materials in control group.Rats were sacrificed 2 weeks and 4 weeks post treatment and samples were cut off for general observation,Micro CT scans and histological observation.Results:General observation showed no new bone formation in Groups A and B mice,while new bones were formed in Groups C and D mice.Two weeks after treatment Micro CT scans showed that The bone volume fraction(BVF),trabecular thickness(Tb. Th),bone mineral density(BMD) in Group C mice were all higher than that in Group D(P<0.05). At the fourth week,the BVK,Tb.Th and BMD were significantly higher than that at the second week(P<0.01).Conclusions:The slow-release effect of rhBMP-2/cs sustained-release capsules can significantly promote ectopic osteogenesis.Its bone formation effect is better than that of rhBMP-2 burst-release group.

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?.

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.

Effects of long-term sustained naltrexone release on the optic center in opioid-dependent patients Case-control study in four provinces of China

Very little is known about visual functional recovery following long-term naltrexone administration in opioid-dependent patients. In the present study, a portable event-related potential （ERP） working system was utilized to collect and record ERP in opioid-dependent patients and normal controls in visual half-field testing. In addition, the influence of long-term sustained naltrexone release on the visual nervous system was observed in opioid-dependent patients. Results revealed a significant main group effect in reaction time to visual signal stimulations. The reaction time of normal controls was shortest, but longest in opioid-dependent patients. The reaction time of long-term sustained naltrexone release group and compulsory detoxification group was similar to normal controls. A significant main group effect was also observed in P100 latency, and P100 latency in normal controls and the compulsory detoxification group was significantly decreased compared with the opioid-dependent patients. P100 amplitude at the Oz-electrode resulted in a significant main group effect. In particular, normal controls exhibited significant differences compared with long-term sustained release naltrexone and compulsory detoxification groups. These findings demonstrated that long-term sustained naltrexone release effectively ameliorated optic center function and improved visual sensitivity and reactions in opioid-dependent patients.