Release Pellets Research Articles

Formulation and in-vitro anticancer activity of nilotinib immediate release and ibrutinib sustained release pellets

Background: Blood cancer is a significant contributor to mortality rates worldwide, and its prevalence is projected to rise on a global scale. This trend places considerable strain on healthcare systems and necessitates the expedited development of innovative treatments by pharmaceutical firms to remain competitive. Conventional pellets produce rapid plasma drug levels, but they might cause side effects, decrease effectiveness, and lead to poor therapeutic management. Ibrutinib and Nilotinib are employed to treat leukemia patients. Methodology: The current research aims to formulate, characterize, and anticancer effect of Nilotinib immediate release (NIR) and Ibrutinib sustained release (ISR) seal sugar-coated pellets. Micrometric properties estimated the characterization of the drug pellets, and surface morphology was estimated using scanning electron microscopy. Drug excipient compatibility studies, stability studies, and in-vitro drug release were accessed. Result & Discussion: The results of pellet formulations FNI-1 to FNI-5 showed that FNI-5 formulations showed 100±6.0 µm size and possessed excellent mechanical strength for giving pellets a good self-life; also, due to the higher drug content up to 99%, FNI-5 was the best suited for pellet formulation and because NIR showed 99.18 ± 2.12 drug release at 2h and ISR 99.03±3.74% up to 12h so that anticancer concentration maintained for prolonged period. The standard dose for cytotoxicity against the THP-1 cell line of Nilotinib was found to be 200 mg, and the maintenance oral dose of Ibrutinib was 140mg, with four times the intake of the drug up to 560 mg. In an in vitro study in FNI-5 (final formulation), the dose of Ibrutinib was reduced to 420 mg. Conclusion: A synergistic effect of Ibrutinib and nilotinib drugs was observed in the inhibition of cancer cell growth, with an IC50 value of 4.585 µg/mL

Preparation and evaluation of lipid-based sustained release pellets of chlorpheniramine maleate by the wet extrusion-spheronization method

Introduction: This study aimed to investigate the feasibility of preparation of sustained-release chlorpheniramine maleate (CPM) pellets based on Compritol® as a lipid matrix and evaluation of the affecting factors on pellet properties. Methods: Using the D-optimal experimental design, different pellet formulations containing various amounts of CPM, Compritol® and Avicel were prepared by the wet extrusion-spheronization method. Then the pellets were cured at 40, 65 and 90 ̊C for 4 and 8 h to study the effect of the thermal process. The physicomechanical properties of the pellets were investigated in terms of particle size distribution, pelletization yield, mechanical strength, aspect ratio and sphericity. To investigate the possible interaction of CPM and Compritol®, as well as to evaluate the morphology and surface characteristics of the pellets DSC and SEM were used, respectively. Also, to investigate the drug release rate from pellets the dissolution test was carried out and mean dissolution time (MDT) was calculated to compare different formulations. Results: The results showed that the curing process up to 65 °C improves the strength of the pellets. However, increasing the curing temperature from 65 to 90 °C and also increasing the curing time from 4 to 8 h did not have a significant effect on the strength of the pellets but increased the drug release rate of pellets. Increasing the amount of the drug or decreasing Compritol® in the matrix of pellets leads to a larger particle size with greater mechanical strength. All formulations of the pellets had an aspect ratio and sphericity of about 1.1 and 0.9 respectively, which indicates the spherical shape of the pellets as shown by SEM. DSC thermograms indicate the reduction of the crystallinity or the change of the crystalline form of the drug to amorphous during the pelletization process. Conclusion: The results revealed the feasibility of preparing lipid-based sustained-release matrix pellets using the wet extrusion-spheronization method. The optimal formulation in terms of physicomechanical properties and release rate was the formulation containing 8% CPM, 67% Compritol® and 25% Avicel, which were dried at 40 ° C for 4 h and released about 90% of the drug within 12 h.

Silencing of ultradian rhythms and metabolic depression during spontaneous daily torpor in Djungarian hamsters

Ultradian rhythms of metabolism, body temperature and activity are attenuated or disappear completely during torpor in Djungarian hamsters, for all three ultradian periodicities (URsmall, URmedium and URlarge). URsmall and URmedium disappear during entrance into torpor, whereas URlarge disappear later or continue with a low amplitude. This suggests a tight functional link between torpor and the expression of ultradian rhythms, i.e. torpor is achieved by suppression of metabolic rate as well as silencing of ultradian rhythms. Spontaneous torpor is often initiated after an ultradian burst of activity and metabolic rate, beginning with a period of motionless rest and accompanied by a decrease of metabolic rate and body temperature. To extend previous findings on the potential role of the adrenergic system on torpor induction we analysed the influence of the ß3-adrenergic agonist Mirabegron on torpor in Djungarian hamsters, as compared to the influence of the ß-adrenergic antagonist Propranolol. Hamsters were implanted with 10 day release pellets of Mirabegron (0.06 mg day−1) or Propranolol (0.3 mg day−1). Mirabegron transiently supressed and accelerated ultradian rhythms but had no effect on torpor behaviour. Propranolol did not affect torpor behaviour nor the expression of ultradian rhythms with the dosage applied during this study.

Preparation and evaluation of lipid-based sustained release pellets of chlorpheniramine maleate by the wet extrusion-spheronization method

Background: This study aimed to investigate the feasibility of preparation of sustained-release chlorpheniramine maleate (CPM) pellets based on Compritol® as a lipid matrix and evaluation of the affecting factors on pellet properties. Method: Using the D-optimal experimental design, different pellet formulations containing various amounts of CPM, Compritol® and Avicel were prepared by the wet extrusion-spheronization method. Then the pellets were cured at 40, 65 and 90 ̊C for 4 and 8 h to study the effect of the thermal process. The physicomechanical properties of the pellets were investigated in terms of particle size distribution, pelletization yield, mechanical strength, aspect ratio and sphericity. To investigate the possible interaction of CPM and Compritol®, as well as to evaluate the morphology and surface characteristics of the pellets DSC and SEM were used, respectively. Also, to investigate the drug release rate from pellets the dissolution test was carried out and mean dissolution time (MDT) was calculated to compare different formulations. Results: The results showed that the curing process up to 65 °C improves the strength of the pellets. However, increasing the curing temperature from 65 to 90 °C and also increasing the curing time from 4 to 8 h did not have a significant effect on the strength of the pellets but increased the drug release rate of pellets. Increasing the amount of the drug or decreasing Compritol® in the matrix of pellets leads to a larger particle size with greater mechanical strength. All formulations of the pellets had an aspect ratio and sphericity of about 1.1 and 0.9 respectively, which indicates the spherical shape of the pellets as shown by SEM. DSC thermograms indicate the reduction of the crystallinity or the change of the crystalline form of the drug to amorphous during the pelletization process. Conclusion: The results revealed the feasibility of preparing lipid-based sustained-release matrix pellets using the wet extrusion-spheronization method. The optimal formulation in terms of physicomechanical properties and release rate was the formulation containing 8% CPM, 67% Compritol® and 25% Avicel, which were dried at 40 ° C for 4h and released about 90% of the drug within 12 h.

Design and Development of Immediate Release Pellets Formulation Containing Co Amorphous Mixture of Aceclofenac: In-Vitro and In-Vivo Study

Design and Development of Immediate Release Pellets Formulation Containing Co Amorphous Mixture of Aceclofenac: In-Vitro and In-Vivo Study

IDF23-0267 Metformin Immediate Release Pellets in Capsule 500 mg (Fasting and Fed)

IDF23-0267 Metformin Immediate Release Pellets in Capsule 500 mg (Fasting and Fed)

FORMULATION AND BIOPHARMACEUTICAL EVALUATION OF SUSTAINED RELEASE PELLETS OF BOSENTAN BY PANCOATING METHOD

Objective: The aim of the present study was to formulate sustained-release pellets of bosentan by eudragit RL 100 and RS 100, which are the polymers used in the pan coating technique. Methods: The sustained release pellets of bosentan were formulated by pan coating method. The drug was coated on nonpareil seeds along with EudragitRL100 by solution layering technique. Drug-loaded pellets were coated with EudragitRS100. The prepared pellets were evaluated for moisture content, drug content, particle size, and in vitro drug release. Stability studies were carried out on the optimised formulations for a period of 6 mo. Results: The drug content was in the range of 98.89±0.32. The mean particle size of the drug-loaded pellets was in the range of 835 μm. The drug release rate decreased as the concentration of eudragit increased in the pellet formulations. Among the prepared formulations, PC 4 showed 89.35±0.52 drug release in 12 h from a good linear relationship was established between model-independent approaches (T25%, T50%, and T100%) and weight gain in coating. This indicated the possibility of extending the drug release by increasing the weight gain in the coating, and hence, it was proposed to extend the drug release for 24 h. From the prepared pellets, the optimised formulation PC 12 showed a 100.02±0.03 drug release in 24 h. Furthermore, these pellets were filled into capsules and compared the dissolution studies. The compatibility between drugs and polymers in the drug-loaded pellets was confirmed by DSC and FTIR studies. Stability studies indicated that the pellets were stable. Conclusion: The prepared pellets were capable of releasing the drug for 24 h to treat the Pulmonary Arterial Hypertension.

Design and Development of Cyclobenzaprine HCl Sustained Release Pellets by Wurster Coating Method

Background Cyclobenzaprine is structurally related to the tricyclic antidepressants. Cyclobenzaprine may be slightly different than the other musculoskeletal agents because it is believed to decrease skeletal muscle spasm through atropine-like effects directly on the cerebral motor neurons. Cyclobenzaprine may also have analgesic properties that may add to its therapeutic effects. This research encompasses all oral dosage forms and strengths.Objective Even though Cyclobenzaprine HCl tablets are available in market we can formulate pellets because pellets demonstrate good flow properties in the intestine and require less cost for the production of formulation. The main aim of the present study was to produce the extended-release Cyclobenzaprine HCl capsules of 16 hours release to reduce the dosing frequency as a skeletal muscle relaxant when compared with the innovator drug Amrix. Cyclobenzaprine HCL is a muscle relaxant that works on the central nervous system by altering the signals from the brain causing muscle to tighten.Methodology Cyclobenzaprine hydrochloride sustained release SR pellets were prepared by Wurster coating method using different excipients and polymers to release the drug slowly for an extended period of time. The method of preparation of Cyclobenzaprine hydrochloride SR pellets involves two steps drug coating and polymer coating. In the drug coating process the drug was coated in a suspension form on the dummy pellets dried and sieved. Drug coated pellets were coated with SR polymer to form SR pellets. These SR pellets were dried sieved and sent for quality control.Results After 12th hour the percentage drug release from the formulations were 89.6 87.4 85.8 85.6 83.9 75.1 for the formulation containing EC N14 2.5 5 7.5 and EC N50 10 12.5 and 15 respectively. The dissolution profile was shown and the mean dissolution time of pellets was noted to be 6.19 hrs. Formulation F5 was identified to be the most superior formulation.Conclusion Accordingly it can be concluded that the F5 12.5 ww EC N50 is a robust one and the performance is less likely to be affected by the various factors studied. The formulations were subjected to stability studies according to the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use ICH guidelines for three months which demonstrated all the tested formulations to be stable.

Pengaruh Desain Punch Terhadap Mutu Fisik dan Disolusi Tablet MUPS Metformin HCl

The compaction of multi-unit pellet system (MUPS) into tablets is a potential alternative for sustained release drugs. Tableting tools (punch and die) affect the compaction process and quality of MUPS tablets. The punch design intends to preserve the desired drug release of compacted pellets. This study aims to investigate the effect of two punch shapes, the flat face radius edge (FFRE) and concave-faced punch (concave), each at two different cup depths, on the physical properties and release profile of metformin HCl MUPS tablets. Drug release parameters, t50 values, showed that the metformin HCl released from MUPS tablets was faster than the uncompacted sustained release pellets. The similarity of the dissolution profile (f2) between MUPS tablets and uncompacted metformin HCl pellets was lower than 50 as the minimum acceptance value. The tablet tensile strength obtained was below the requirements (<1.7 MPa). Tablet disintegration time was approximately less than 2 minutes. In conclusion, drug release profile of the MUPS tablets showed damage of the pellets due to compaction process. Nevertheless, pellets compacted at low compaction pressure using FFRE with a deeper cup depth (size 0.80 mm) showed a slightly better protection compared to other punch shapes and cup depth sizes applied.

Design, Development and In-Vitro Characterization of of Cyclobenzaprine Hcl Sustained Release Pellets

The aim of the present studyisto formulate and evaluate the cyclobenzaprine hydrochloride extended release pellets by Wurster coating method using starch, PVP K-90, ethyl cellulose, isopropyl alcohol, talc and other polymers to release the drug slowly through an extend period of time. The method of preparation of Cyclobenzaprine Hydrochloride SR pellets involves in two steps, namely drug coating and polymer coating. In the drug coating process drug is coated as a suspension form to dummy pellets and dried and sieved. Drug loaded pellets are coated with SR polymer to form SR pellets. These SR pellets are dried, sieved and send to quality control.FTIR studies of the formulation indicating no chemical interaction between cyclobenzaprine HCl and excipients. In order to get the optimized formulation, the various process parameters were adjusted. The various evaluations for formulations were carried out, that to based on the in-vitro drug release studies of F5 formulation shows better drug releaseprofile than other formulations. The results conclude that trial F5 has met the objective of extended release, cost effective as once day of drug.

Long-term normalization of calcineurin activity in model mice rescues Pin1 and attenuates Alzheimer’s phenotypes without blocking peripheral T cell IL-2 response

BackgroundCurrent treatments for Alzheimer’s disease (AD) have largely failed to yield significant therapeutic benefits. Novel approaches are desperately needed to help address this immense public health issue. Data suggests that early intervention at the first stages of mild cognitive impairment may have a greater chance for success. The calcineurin (CN)-Pin1 signaling cascade can be selectively targeted with tacrolimus (FK506), a highly specific, FDA-approved CN inhibitor used safely for > 20 years in solid organ transplant recipients. AD prevalence was significantly reduced in solid organ recipients treated with FK506.MethodsTime release pellets were used to deliver constant FK506 dosage to APP/PS1 mice without deleterious manipulation or handling. Immunofluorescence, histology, molecular biology, and behavior were used to evaluate changes in AD pathology.ResultsFK506 can be safely and consistently delivered into juvenile APP/PS1 mice via time-release pellets to levels roughly seen in transplant patients, leading to the normalization of CN activity and reduction or elimination of AD pathologies including synapse loss, neuroinflammation, and cognitive impairment. Pin1 activity and function were rescued despite the continuing presence of high levels of transgenic Aβ42. Indicators of neuroinflammation including Iba1 positivity and IL-6 production were also reduced to normal levels. Peripheral blood mononuclear cells (PBMC) obtained during treatment or splenocytes isolated at euthanasia activated normally after mitogens.ConclusionsLow-dose, constant FK506 can normalize CNS CN and Pin1 activity, suppress neuroinflammation, and attenuate AD-associated pathology without blocking peripheral IL-2 responses making repurposed FK506 a viable option for early, therapeutic intervention in AD.

Estrogen promotes the proliferation and migration of endometrial cancer cells by upregulating the expression of lncRNA HOTAIR

Objective Estrogen (E2) is the main contributor to the progression of endometrial cancer (EC). The long noncoding RNA HOX antisense intergenic RNA (HOTAIR) is emerging as a new regulator in several cancer types. This study aimed to investigate the role of HOTAIR in EC development and identify the underlying molecular mechanisms. Methods HOTAIR expression levels in human EC tissues and the corresponding adjacent tissues and human EC Ishikawa cells were determined by quantitative PCR. Ishikawa cells were treated with E2 or estrogen receptor (ER) inhibitor ICI182780, transfected with siHOTAIR oligo, or infected with lentivirus expressing shHOTAIR/shNC, alone or in combinations. The protein expression of polycomb repressive complex 2 (PRC2) was evaluated by western blotting, and cell migration was measured by transwell assays. A xenograft tumorigenic model was established by inoculating control or stable shHOTAIR-infected Ishikawa cells into nude mice and implanting 17β-estradiol release pellets. Results HOTAIR expression was significantly elevated in human EC tissues. E2 exposure markedly increased HOTAIR levels in Ishikawa cells. Notably, E2 increased the protein expression of PRC2 and promoted EC cell migration, which were dependent on HOTAIR expression, as HOTAIR knockdown abolished these effects of E2. Similarly, E2 promoted the in vivo proliferation of grafted Ishikawa cells via upregulated HOTAIR expression in nude mice. Conclusions Human EC tissues highly express HOTAIR, and E2-induced EC progression depends on HOTAIR expression. This work suggests that the E2-HOTAIR axis is a potential therapeutic target in EC therapy.

Optimization and evaluation of Lisinopril mucoadhesive sustained release matrix pellets: In-vitro and ex-vivo studies

Lisinopril (LIS) is antihypertensive drug, classified as a class III drug with high water solubility and low permeability. To overcome the low permeability, 32 factorial designs aimed to formulate LIS as a sustained-release (LIS-SR) matrix pellet by extrusion/spheronization. Matrix pellets were composed of wet mass containing Avicel® and polymeric matrix polymers (sodium alginate (SA) and chitosan (CS)). Evaluation of the effect of two independent variables, matrix-forming units (SA and CS) on mean line torque, on pellet size, dissolution rate after 6 h, and mucoadhesion strength of the pellets were assessed using Statgraphics software. The tested formulations (F1-F9) showed that mean line torque ranged from 1.583 to 0.461 Nm, with LIS content in the LIS-SR pellets ranged from 87.9 to 103%, sizes varied from 1906 to 1404 µm and high percentages of drug released from pellets formulations (68.48 to 74.18 %), while the mean zeta potential value of mucoadhesive range from −17.5 to –22.9 mV.The selection of optimized formulation must have the following desirability: maximum peak torque, maximum pellets’ particle size, and minimum % LIS release after 6hr. LIS optimized sustained release pellet formula composed of 2,159 % SA and 0.357 % CS was chosen as optimized formula. It’s showed a 1.055 Nm mean line torque was responsible for the increased pellet size to 1830.8 μm with decreased release rate 56.2 % after 6 hr, and −20.33 mV average mucin zeta potential.Ex-vivo mucoadhesion studies revealed that that the optimize formulation, exhibited excellent mucoadhesive properties, after 1 h, about 73% of the pellets were still attached to the mucus membrane. Additionally, ex-vivo permeation determination of LIS from the optimized LIS-SR formulation was found to be significantly higher (1.7-folds) as compared to free LIS.In conclusion: LIS-SR matrix pellets, prepared with an extrusion/spheronization have desirable excellent characteristics in-vitro and ex-vivo sustained-release pellet formulation of LIS-SR was able to sustain the release of LIS for up to 8 h.

Pharmaceutical Micropellets: A Multi-particulate Drug Delivery System

Abstract: The major target of Pharmaceutical Sciences is to design a successful and suitable dosage forms for effective therapy, considering individual patient needs and compliance. Development of new technology or development of new dosage form using the existing technology is growing in importance and attracting increased interest, as they are specifically effective at a comparably low dose. Pellets falling in the size range of 1-1000μm are of great interest in the pharmaceutical industry for a variety of reasons which are not only offer flexibility in dosage form design and development, but are also utilized to improve the safety and efficacy of bioactive agents. The most important factor responsible for the proliferation of pelletized products is the popularity of controlled release technology in the delivery of drugs. Moreover, controlled release pellets are less susceptible to dose dumping than the reservoir-type single unit formulations. In case of oral products these pellets solve difficult taste-masking problems, disperse freely in the gastro intestinal tract, invariably maximize drug absorption, reduce peak plasma fluctuations and minimize potential side effects without appreciably lowering drug bioavailability, and also reduce variations in gastric emptying rate and overall transit time, thus, intra and inter subject variability of plasma profiles, which are common with single unit regimens, are minimized.

Abstract P4-01-24: Targeting receptor tyrosine kinases in overcoming tamoxifen resistance and dormancy in invasive lobular cancer

Abstract Objective: The molecular hallmark of invasive lobular cancer (ILC) is the loss of E-cadherin, resulting in the unique morphology, low mitotic index and unusual metastatic spread to ovaries, gut, and peritoneum. Patients with ILC face delayed, and higher stage at diagnosis, worse disease-free and overall survival1. The most frustrating challenge is the delayed recurrence, likely due to resistance and induction of dormancy2. Despite these unique features, ILC is lumped with hormone receptor-positive invasive ductal cancers (IDC); consequently, management strategies are based on data from IDC. Hence there is an unmet need to address the unique challenges of ILC. We generated Tamoxifen-resistant (TAMR) ILC cell lines with the aim to study the distinct characteristics, dormancy, differentially activated pathways, and response to drugs targeting such pathways in the resistant cells. Methods: We used MDA-MB-134-VI and SUM44-PE cells to study the effect of tamoxifen in combination with multi-targeted receptor tyrosine kinase inhibitor, Lenvatinib. TAMR cells from both MB-134 and SUM44PE cells were generated by growing them in increasing concentrations of 4-hydroxy tamoxifen (4-HT) up to 500nM, for 6 months. Total RNA from parental and TAMR cells were subjected to RNA-seq. Whole cell extracts were analyzed for specific phospho proteins by Western Blot analysis. Growth kinetics and effect of drugs on cell viability was measured using MTT assay (Roche). Cell migration was measured using Transwell migration assay. Novel engineered 2D and 3D cultures were used to study dormancy and the effect of the drug combination. Orthotopic tumor induction in NSG mice is ongoing to determine the effect of drug combination in vivo. Results: The TAMR cell lines show distinct morphological features, small but significant increase in growth rate (p=0.05) and remarkably higher migration (MB-134TAMR:11.5-fold, p< 0.005 and SUM44TAMR:>100-fold, p< 0.005). The IC50 for tamoxifen increased from 8.1M (MB-134) to 16.8M (MB-134TAMR) and from 11.3 M (SUM44) to 26.6 M (SUM44TAMR). RNA seq analysis revealed enrichment of PI3K-AKT, MAPK, cAMP, Rap1 signaling pathways, ECM-receptor interaction, Focal adhesion, and steroid hormone biosynthesis pathways in the TAMR cells. Upon stimulation by endothelial growth factor, the MB-134TAMR but not the parental cells showed dose dependent increase in phospho-AKT and phospho-MAPK levels. Using novel 2D/3D cultures, we show differential morphologies between IDC (MCF7) cells, MB-134TAMR, and the parental cells. MCF7 and MB-134TAMR cells are more adherent to fibronectin (p< 0.0001), whereas the parental ILC cells are more adherent to COL3A1 (p< 0.0001), a feature observed in dormancy3. Further, the administration of 5 M 4-HT induced a cessation of growth in the parental cell line, with a sub-population of apparent dormant cells. The combination of Lenvatinib (5 M) and 4-HT (7.5 M) synergistically inhibited both the parental cell lines by ~60%. Lenvatinib (5 M) and 4-HT (15 M) inhibited the MB-134TAMR and SUM44TAMR cell lines synergistically by 65% and 45% respectively. In vivo, the growth of MB-134 induced tumors were completely suppressed when 5mg sustained release pellet of TAM citrate was injected in the subscapular region of tumor bearing mice (tumor @100cm3). The results of the combination using in vivo models and 2D/3D cultures will be reported. Conclusion and significance: Lenvatinib with tamoxifen is active and synergistic against parental and TAMR ILC cell lines. Our novel 2D/3D cultures show distinct pattern of growth for ILC cells and a possible induction of a dormant subpopulation upon 4-HT treatment. Overcoming resistance to conventional therapies and preventing induction of dormancy will improve long-term outcomes of patients with ILC. 1. PMID:33641217 2. PMID: 34388695 3. PMID: 35121989 Citation Format: Bhuvaneswari Ramaswamy, Nikhil Pramod, Anagh Kulkarni, Xilal Y. Rima, Eduardo Reátegui, Eswar Shankar, Sarmila Majumder. Targeting receptor tyrosine kinases in overcoming tamoxifen resistance and dormancy in invasive lobular cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-01-24.

Developing novel persulfate pellets to remediate BTEXs-contaminated groundwater

Organic-contaminated groundwater poses a growing threat to environmental sustainability and human health. As a passive plume control technology, permeable reactive barriers (PRBs)have become a popular method for groundwater pollutants degradation due to their cost-effective and sustainable merits. However, active materials adopted in conventional PRBs have the shortcomings of easy deactivation and speedy consumption. As an alternative, slow-release materials can be used as PRBs fillers to treat contaminated groundwater because of their long chemical release time. In this study, novel slow-release persulfate pellets were prepared and tested for their release capabilities and effectiveness in the remediation of groundwater organic pollution. Results show that each pellet's release efficiency and average release rate within 14 days were 87.36 % and 46.80 mg-persulfate/d, respectively, when the mass ratio of sodium persulfate to paraffin was 3/1. Dissolution and diffusion via pores are the main mechanisms of the persulfate delivery from slow-release pellets in water. Moreover, solution pH, ionic species and addition of quartz sand into release pellets play dissimilar effects on the release kinetics. Results from column experiments indicate that the pellets could expand the PS influence range in the barrier and continuously remediate BTEXs-contaminated groundwater (initial concentration of each compound = 50 mg/L) and reach 64.2–85.1 % removal efficiency. The results of electron spin resonance (ESR) spectroscopy show that both SO4− and OH contribute to the removal of BTEXs. This study demonstrates the potential feasibility of slow-release persulfate materials for groundwater pollution treatments by PRBs, which inspires for future field applications.

Optimization of Preparation Process and Pharmacokinetics of APAP Double-Release Pellet Capsules

In order to develop a kind of APAP double-release pellet capsules, which was prepared with the manual filling method, the immediate and sustained release pellets of a certain proportion were prepared by the fluidized bed coating and the extrusion spheroidization process, respectively. It was founded that both the prepared immediate-release pellets and sustained-release pellets had smooth and round surfaces. The particle size distribution ranged evenly from 16 to 35 mesh. Response surface plots showed that the optimal preparation prescription for immediate-release pellets were that ethanol concentration (X1) 70%, APAP 20%, MCC (X2) 40%, PVP K30 (X3) 20%, and sucrose pellet core 20%; and the optimal preparation prescription for sustained-release pellets were that HPMC concentration (X*3) 6.5%, APAP 30%, EC (X*1) 20%, MCC (X*2) 40%, PVP K30 4%, and lactose 6%. The results of pharmacokinetic analysis revealed that, after the APAP double-release pellet was orally administered, compared with that of conventional tablets, the plasma APAP levels in the blood circulation dramatically rose to significant peaks as a result of the quick and slow release of APAP from the capsules, which significantly prolonged the effective time of drugs in blood. Finally, immediate and sustained antipyretic-analgesic effects were obtained.

Preparation, characterization, and in vitro release of microencapsulated essential oil hydroxyapatite pellets filled into multifunctional capsules

Oregano essential oil (EO)–loaded pellets were prepared using calcium phosphate substrates of different specific surface areas (Sw) and as binders EO in water emulsions with low or high EO content, stabilized with polysaccharides (PSC) or a combination of PSC-Eudragit® L100-55 (PSC-PLM) encapsulants. Tri-cafos® 250 with high Sw gave higher EO loading and more spherical pellets with narrow size distribution. These were filled into the following hard-shell capsules: gelatin, hydroxypropyl-methyl cellulose (HPMC) based immediate release (Vcaps® plus), gastro-resistant (DRcaps®) and enteric release (Vcaps® enteric), and pullulan (Plantcaps®). FTIR and Raman spectroscopy showed H-bonding between PSC and EO and between PSC and PLM. Pellet mechanical strength decreased with EO content and pellets made with PSC emulsions were stronger than PSC-PLM pellets proving PSC binder ability. Disintegration and release of EO from capsules filled with immediate release pellets (PSC) or enteric pellets (PSC-PLM) were tested sequentially in pH 1.2 and 6.8. Capsule shell influenced disintegration and release. The release of EO from the PSC pellets within 1 h, at pH 1.2 was from gelatin 82%/85% (for low/high EO emulsions) but from Vcaps® plus and Plantcaps® it was lower, 36%/38% and 45%/70% respectively. DRcaps® and Vcaps® enteric capsules confirmed gastro-resistance. The release of enteric (PCS-PLM) pellets was: from gelatin and Vcaps® plus capsules 21%/23% and 20%/21% respectively, but from Plantcaps® 61%/62%, indicating deactivation of Eudragit® L100-55 functionality in the last case. In all cases, release was complete after 180 min, but release of enteric pellets from Vcaps® plus was slower than from gelatin capsules due to the presence of HPMC.

Effects of estradiol on dopaminergic synapse formation in the mouse olfactory bulb.

Olfactory glomeruli are the sites of initial synaptic integration in olfactory information processing. They are surrounded by juxtaglomerular (JG) cells, which include periglomerular, superficial short axon, and external tufted cells. A subpopulation of JG cells expresses the dopamine synthetic enzymes, tyrosine hydroxylase (TH), and aromatic l-amino acid decarboxylase (AADC). TH cells corelease γ-aminobutyric acid (GABA) and their processes extend to multiple glomeruli forming intra- and interglomerular circuits. It is well established that 17β-estradiol (E2) exerts wide ranging effects in the central nervous system. However, participation of E2 in the modulation of neurotransmission and synaptic plasticity of TH cells in olfactory glomeruli is unknown. To address this, we subcutaneously implanted a 60-day release pellet of E2 or placebo into intact male mice and compared glomerular TH, AADC, and vesicular γ-aminobutyric acid transporter (VGAT) immunoreactivity between them. High-voltage electron microscopy (HVEM) and ultra-HVEM using immunogold revealed significantly increased immunoreactive intensity at the cellular level for TH and AADC after E2 treatment and for VGAT in TH cells. These results indicate that E2 may affect the interplay between dopaminergic and GABAergic systems. Moreover, random-section electron microscopy analysis showed a significant increase in the number of symmetrical synapses from TH cell to mitral/tufted cell dendrites after E2 treatment. This result was supported by quantitative immunofluorescence staining with synapse markers. Together, these data indicate that E2 may regulate inhibition between TH cells and olfactory bulb neurons within the glomerulus via interaction between dopaminergic and GABAergic systems, thereby contributing to neuromodulation of odor information processing.

Formulation and Evaluation of Sustained Release Pellets of Verapamil HCL

Verapamil Hydrochloride, an antihypertensive agent which is used as a calcium channel blocker. The aim of the present study was to formulate and evaluate Verapamil HCL sustained release pellets. The work is to obtain Verapamil HCL sustained release pellets by using HPMC based polymers i.e., HPMC AN6, HPMC E5, HPMC E15 in the sustained release layer. The verapamil Hydrochloride has pH-dependent solubility. To overcome the pH dependent solubility Fumaric acid was used that which provides micro-acidic environment. Different Ratios of Ethyl-cellulose and HPMC polymers were used to optimise and evaluate the formulation for the sustained release of the drug. It uses the Pelletization technology. This technique is practised to produce pellets of uniform size with high drug loading capacity and also to prevent the segregation and dust.