Pellet Formulation Research Articles

Formulation optimization of solid self-microemulsifying pellets for enhanced oral bioavailability of curcumin

Solidification of self-microemulsifying drug delivery systems (SMEDDS) is one of the major trends to promote the transformation of self-microemulsion technology into industrialization. Here, a preliminary curcumin SMEDDS formulation was constructed to improve the druggability of curcumin, through the determination of equilibrium solubility determination, self-emulsifying grading assessment, and pseudo-ternary phase diagrams drafting. Furthermore, the optimal curcumin SMEDDS formulation consisted of 10% Ethyl oleate, 57.82% Cremophor RH 40, and 32.18% Transcutol P was obtained by the simplex lattice design. Besides, curcumin solid self-microemulsifying drug delivery system (S-SMEDDS) was developed by the extrusion and spheronization process to achieve the solidification of SMEDDS. The formulation of curcumin S-SMEDDS pellets was screened by the single factor experiment and the process parameters were investigated using the orthogonal optimization method. Subsequently, curcumin S-SMEDDS pellets were evaluated by apparent morphology characterization, redispersibility study, drug release behavior, and pharmacokinetic evaluation. Results from the pharmacokinetic study in rabbits showed that the AUC0–τ of the curcumin S-SMEDDS pellets and curcumin suspension were 5.91 ± 0.28 µg/mL·h and 2.05 ± 0.04 µg/mL·h, while the relative bioavailability was 289.30%. These studies demonstrated that S-SMEDDS pellets can be a promising strategy for curcumin industrialized outputs.

Computational predictability of polyethylene glycol encapsulated modified release multiple unit pellets formulation of metoprolol succinate using different multivariate models

ABSTRACT The present investigation was computational predictability of Polyethylene Glycol (PEG) encapsulated modified release multiple unit pellets system (MUPS) tablet of Metoprolol succinate by quality by design (QbD). Quality target product profile (QTPP) and critical quality attributes (CQAs) of MUPS tablets were defined. Risk assessment was done using Ishikawa diagram and failure mode effect analysis (FMEA) as per ICH Q8 guidelines. Formulation was screened and optimized using Plackett–Burman and Box– Behnken design. Pellets were prepared by wruster coating system-using polymers such as hydroxypropyl methylcellulose (HPMC), Ethyl cellulose (EC) with other excipients. Formulation variables X1: HPMC and X2: EC have affected the drug release (Y1). PEG capsulation ensures the intactness of film after compression. ANOVA results confirm the selected model was statistically significant. This investigation demonstrated the PEG encapsulated HPMC and EC polymer coated with optimised curing time will achieve a single dose of metoprolol succinate applying QbD.

The effectiveness of bioherbicide made from nutsedge tuber powder (Cyperus rotundus l.) in various dosage and application time

Nutsedge (Cyperus rotundus L.) is a very adaptive weed, therefore it is very difficult to be controlled. Besides, the Cyperus rotundus has allelopathic compounds that can interfere with the growth of the main plant. The allelopathic compound has the potential to be used as a pre-emergence bioherbicide for controlling broadleaf weeds and grass. The aim of this study was to determine the effectiveness of bioherbicides made from nutsedge tuber powder sources at various dosage and application times. This research was conducted from August to October 2019, used CRD with three replications. The first factor was the dosage (D); 45.00 and 67.50 kg powder ha−1. The second factor was the application of time (T); 2 DBP, 0, 2, 4 DAP so that there were 8 treatment units. The result showed that the application of bioherbicides made from nutsedge tuber powder with pellet formulations on 0 to 4 DAP was effective in inhibiting the germination and growth of all test weeds, the best application time varies between test weeds. In general, a dosage of 67.50 kg tuber powder ha−1 was more effective in inhibiting germination and growth of weed sprouts as compared to a dosage of 45.00 kg tuber powder ha−1.

Development and characterization of enteric coated pectin pellets containing mesalamine and Saccharomyces boulardii for specific inflamed colon: In vitro and in vivo evaluation

The objective of this study was to develop and characterize enteric-coated pectin pellets containing mesalamine and S.bulardii for specific colon targeted drug delivery for ulcerative colitis management. Pellets of mesalamine and S.bulardii were produced by extrusion-spheronization technique by using pectin and microcrystalline cellulose and coated with Cellulose acetate phthalate. The pellets were evaluated for morphology, micromeritic properties as well as through fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray diffraction techniques and the results confirmed that all the ingredients of the pellets were compatible with each other without revealing any specific interaction. The dissolution profiles of uncoated and coated pellets were examined at pH 1.2, 6.8 and 7.4 with and without rat cecal content. Further pharmacokinetic studies revealed a lower value of maximum concentration in the case of cellulose acetate phthalate coated pellets formulation in comparison to uncoated ones which, evidenced the lower systemic exposure of the drug. Finally, to ensure the therapeutic activity of the selected formulation, a 2,4,6-trinitrobenzene sulfonic acid-induced colitis model was used. Colon/Bodyweight ratio, myeloperoxidase, lipid peroxidase level, glutathione activity and histological evaluation were performed in the colitis model. Animal experiments revealed that coated pellets of mesalamine and S.bulardii significantly improved the diseased conditions in Wistar rats. The confirmation of which was done by the gain in weight, clinical improvement in macroscopic and microscopic factors of induced colitis. These findings ensure that coated pellet formulation has promising potential for targeted drug delivery of mesalamine and S.bulardii to the colon as well as to improve the viability of probiotics and enhancement in the effectiveness of mesalamine in management of ulcerative colitis.

Formulation and In-Vitro Evaluation of immediate-release pellets of Candesartan Cilexetil

Multi particulate drug delivery system has long run also been made use of to enhance the overall bioavailability going from drugs having low aqueous solubility. Candesartan Cilexetil is an anti-hypertensive drug. Complex and dispersion of Candesartan Cilexetil with the different carriers were prepared to increase its solubility and bioavailability. Due to its low aqueous solubility bioavailability of the drug is 15 % and it shows variable absorption from GIT. Pellets offer several advantages such as proper distribution in the GIT tract, reduces dose dumping, and relief going from administration as well as closing going from chemotherapy therefore within the time being work an immediate-release Pellets of candesartan cilexetil was planned out using the representational of increasing the solubility and in turn bioavailability of Candesartan Cilexetil. Immediate release Pellets containing complex or dispersion of Candesartan Cilexetil with the suitable carrier was prepared using non-pareil sugar seeds. On the non-pareil seeds, drug layering of Candesartan Cilexetil complexed or dispersed with the suitable carrier was done. The formulation having Candesartan Cilexetil and Eudragit dispersed in 1:3 ratios is considered the best product concerning assay and in-vitro drug release. The present top of the line used to be promote withstand constancy written report, the results of and that indicated no important change concerning assay, content uniformity, and in vitro drug release.

New κ-Carrageenan-montmorillonite Polyelectrolyte Complex used as a Polymer for the Extended Release Circular Pellets Containing Tapentadol Hydrochloride: Statistical optimization

ABSTRACT The present investigation aims at development of extended release (ER) pellets using κ-carrageenan-montmorillonite (κ-Carr-MMT) polyelectrolyte complex (PEC) hydrogel. The PEC was used as binder and ER polymer, whereas tapentadol was a model drug. The hydrogels were optimised using 32 full factorial design and characterised by FTIR, DSC, XRPD, and SEM analyses. The pelletisation was done using extrusion-spheronization procedure. The prepared pellets were further characterised for yield, FTIR, DSC, XRPD, pellet morphology, flow characteristics, mucoadhesion, and in vitro drug release studies.The interactions between the cationic silicate hydroxylated edge groups of MMT with the anionic sulphate group of κ-carrageenan leads to the formation of κ-Carr-MMT PEC hydrogel and these interactions were confirmed by FTIR analysis. The optimised pellet formulation containing 2.25:1.00 ratio of κ-Carr and MMT exhibited sustained drug release upto 12 h, in vitro. Present ER pellet formulation could be a best alternative to the conventional formulations for pain management.

Design and optimization of pellets formulation containing curcumin ascorbic acid co-amorphous mixture for ulcerative colitis management

Curcumin is known for its various therapeutic properties like anti-inflammatory, antioxidant, anticancer, however, its oral use is restricted due to its low solubility and dissolution rate in alkaline pH. In this study co-amorphous mixture of curcumin–ascorbic acid (CU:AA) of different molar ratios was prepared using the ball milling method. The solubility and characterization of the mixture were studied using FTIR, DSC, and XRD study. Mixture (1:0.50) molar ratio showed the highest solubility and was formulated in pellets dosage and optimized using 32 full factorial designs. The solubility results revealed that a significant increase (p < 0.005) in the solubility of curcumin by the ratio 1:0.50 (212 ± 12 µg/ml) compared to the pure drug (90.0 ± 10 µg/ml). XRD and DSC studies confirmed the formation of amorphous curcumin, whereas FTIR elucidated weak hydrogen interactions. In-vitro dissolution study results showed the (CU:AA) ratio (1:0.50) higher percent drug release (81.61 ± 5.12%) compared to the pure drug (19.44 ± 4.60%). The developed formulations are found to be stable. Therefore, the prepared pellets of co-amorphous mixture enhance the solubility, dissolution rate, and stability of curcumin in higher pH, which will become a promising approach for combination therapy in the treatment of ulcerative colitis patients.

Characterization of transport mechanisms for controlled release polymer membranes using focused ion beam scanning electron microscopy image-based modelling

Mass transport mechanisms of drug release inside a pellet formulation through polymer membrane were investigated with focused ion beam scanning electron microscopy (FIB-SEM). Through careful control of imaging conditions, sub-surface cross sectional images were acquired on two controlled release membrane samples. Image analysis of porosity, pore size distribution, and pore connectivity in 3D provided a matrix of parameters to quantitatively compare samples from different formulations and processing conditions. Image-based computational fluid dynamics simulations were employed to correlate membrane microporosity with flow permeability. Through high resolution FIB-SEM characterization, quantitative microporosity analysis, and mechanistic investigations of flow via image-based simulations, it was found that a 10% difference in the water content of the mixed aqueous-organic solvent used to dissolve polymers had a significant impact on the controlled release performance. This approach provides an analytical avenue to evaluate effects of permeation enhancers, solvents, and other process conditions on controlled release formulations.

Systematic Development of Bicalutamide Immediate Release Pellets Using Aeroperl and Non-MCC Extruder Aid

Background: The Microcrystalline Cellulose is called as a gold standard for the manufacture of pellets. The poor disintegration leads to incomplete drug release that restricts the use of MCC in the immediate-release formulation. Objective: The present work aims to explore non-MCC extruder aid for pellet formulation and solubility modulation potential of Aeroperl® 300 Pharma. Methods: Bicalutamide (BCL) was selected as a model BCS class-II drug. The solubility of BCL was assessed in different vehicles such as polyethylene glycol, propylene glycol, and Tween by carrying out phase solubility study. The suitable vehicle was selected based on the higher solubility of BCL. The vehicle was further adsorbed on newer adsorbent Aeroperl® 300 Pharma to formulate liquisolid granules. The liquisolid granules were further incorporated into the pellet using mannitol and microcrystalline cellulose as an extruder aid. Box-Behnken design was adopted for the optimization of formulation considering MCC: mannitol ratio, the concentration of HPMC and spheronizer speed as independent factors whereas drug release at 30 min, disintegration time and aspect ratio were selected as dependent variables. The pellets were evaluated for different evaluation parameters. Results: Propylene glycol was selected for the formulation of liquisolid technique based on the results of the phase solubility study. Propylene glycol containing BCL was adsorbed on Aeroperl 300 Pharma. The optimized batch was selected exploring the Design-Expert software by considering the limits of different responses. Pellet had excellent flowability. Friability was found to be within the range (&lt;1%). Pellets were found to be spherical and had pores on the surfaces. Conclusion: Liquisolid granules containing newer solubilizer Aeroperl was found to be a promising approach for the improvement in the solubility of the drug. The use of mannitol with MCC has a profound effect on disintegration time, without altering flow property and other parameters. No patents were reported on the combination of Bicalutamide, mannitol and Aeroperl. The critical finding of the present work is to use mannitol as an extruder aid to fasten the disintegration leads to complete drug release within a short period of time. Aeroperl and Mannitol, MCC: mannitol ratio, the concentration of HPMC and spheronizer speed were found to be significant and had the potential effect in pellet formulation.

Keefektifan Bioherbisida Berbahan Baku Tepung Umbi Teki (Cyperus rotundus L.) pada Berbagai Formulasi dan Dosis

Teki (Cyperus rotundus L.) merupakan salah satu gulma berbahaya pada komoditi hortikultura karena mengandung alelokimia yang dapat menghambat perkecambahan tumbuhan. Alelopati tersebut berpotensi untuk digunakan sebagai bioherbisida pratumbuh untuk mengendalikan gulma berdaun lebar dan rumput. Tujuan penelitian adalah untuk mengetahui keefektifan bioherbisida berbahan baku umbi teki pada berbagai formulasi dan dosis. Percobaan ini dilaksanakan pada bulan Maret sampai Juni 2019 di rumah kaca Kebun Percobaan Cikabayan, IPB University, Bogor, untuk penanaman biji gulma. Penelitian menggunakan rancangan rancangan acak lengkap faktorial dengan tiga ulangan. Faktor pertama adalah formulasi umbi teki (F1: tepung umbi teki, F2: tepung umbi teki + aquades, F3: tepung umbi teki + aquades + surfaktan, F4: maserat, F5: maserat + surfaktan, dan F6: pellet), dan faktor kedua adalah dosis (D1: 22.50 kg tepung ha-1, D2: 45 kg tepung ha-1, dan D3: 67.50 kg tepung ha-1) sehingga terdapat 18 unit perlakuan. Hasil percobaan menunjukkan bahwa semua formulasi bioherbisida berbahan baku tepung umbi teki efektif menekan perkecambahan. Formulasi pellet merupakan formulasi yang direkomendasikan karena dalam pengaplikasiannya lebih mudah dan efisien. Dosis efektif untuk menekan perkecambahan dan pertumbuhan kecambah tanaman uji adalah 45 kg tepung ha-1.&#x0D; Kata kunci : A. gangetica, A. gangeticus, E. crus-galli, maserasi, pellet

Acute and chronic oral toxicity assessment of longan sugar extracts derived from whole fruit and from fruit pulp in rats

Ethnopharmacological relevanceLongan (Dimocarpus longan Lour.) is one of the most popular subtropical fruits. Various parts of longan, including seeds, pericarp and pulp, have long been used in traditional medicine in China, Thailand and other Asian countries. The pulp has high sugar, vitamin and mineral content as well as bioactive components. The seeds and pericarp have also been reported to contain beneficial polyphenolic compounds. Longan sugar extract from pulp (LGSP) is prepared as a conventional sugar product. Longan sugar extract from whole longan fruit (LGSW) is also offered as a health food and as a medicinal product. Aim of the studyThe objective of this study was to identify and compare potential health hazards of both LGSW and LGSP by testing for acute and chronic oral toxicity in rats. Materials and methodsIn acute toxicity testing, an oral dose (20 g/kg) of either LGSW or LGSP was administered to groups of rats. Mortality and clinical signs of toxicity were observed for 24 h, and then daily for a total of 14 days. In the chronic toxicity test, either LGSW (1, 2.5 and 5 g/kg/day) or LGSP (5 g/kg/day) was administered orally for a period of 180 days. After that treatment period, the rats in the satellite groups which received the highest doses of either LGSW or LGSP were observed for an additional 28 days. The rats then underwent clinical observation, body and organ weight measurement, hematological and biochemical analyses, and histopathological examination. ResultsIn the acute toxicity study, the oral administration of LGSP or LGSW in either pellet or syrup formulations did not cause mortality or any pathological abnormalities. In the chronic toxicity study, neither LGSW nor LGSP resulted in death or in any changes in behavior of the rats. All hematological and serum biochemical values of both the LGSW- and LGSP-treated groups were within the normal ranges. No histopathological abnormalities of any internal organs were observed. ConclusionThe safety of longan sugar extract made from whole fruit (pulp, seeds and pericarb) is comparable to that of longan sugar extract made from pulp alone.

Optimized flurbiprofen sustained-release matrix pellets prepared by extrusion/spheronization

Flurbiprofen (FBP) is an ibuprofen derivative with less gastric side effects and short biological half-life (4.7–5.7 h). The study aimed to formulate FBP as a sustained-release pellets by extrusion/spheronization to overcome its short half-life and to decrease dose frequency. The wet mass of the pellets containing Avicel® and a polymeric matrix polymer was determined by measuring the mean line torque. The impacts of different types and concentrations of matrix-forming units (HPMC, Carbopol, and PVP) (independent variables) on pellet size, mean line torque, and dissolution rate after 8 h were assessed using the Box-Behnken design. The results showed that the formulation containing higher concentrations of HPMC and Carbopol, such as F14, had high mean line torque value. This high mean line torque was responsible for the increased pellet size (>1100 μm) and decreased release rate (68 ± 2.8%) after 8 h of F14, compared with those of F5, which did not contain HPMC or Carbopol and had the lowest mean line torque, smallest pellet size (875.9 ± 27.5 μm), and highest dissolution rate after 8 h (100 ± 5.9%). In conclusion, sustained-release pellet formulation of FBP was able to sustain the release of FBP for up to 8 h.

Predatory effects of the fungus Arthrobotrys cladodes on sheep gastrointestinal nematodes

ABSTRACT The biological control of gastrointestinal nematodes of animals using nematophagous fungi is considered a promising approach. The objective of this study was to evaluate the effectiveness of Arthrobotrys cladodes (CG 719) isolates in vitro and after passage through the gastrointestinal tract of sheep. In experiment 1, the in vitro predatory capacity of A. cladodes against gastrointestinal nematodes in sheep was evaluated. Petri dishes containing fungi cultured on water agar medium were inoculated with 2,000 infective larvae of sheep gastrointestinal nematodes. Experiment 2 involved treatment and control groups comprising six sheep each. The animals in the treatment group received single 10 g doses of pellets containing fungal formulations, and fecal samples were collected after 12, 24, 36, 48, 60, and 72 h. In experiment 1, a larval reduction of 72.3% was observed at 7 days after the larval inoculation. In both assays of experiment 2, larval reductions were significant (p < 0.01). In assay A, this fungus was able to pass throught the gastrointestinal tract of sheep, with a larval reduction of 83.5%. In assay B, proportion of larvae recovered from coprocultures was reduced by 72.4%. Thus, we concluded that pelleted formulations of A. cladodes were effective against gastrointestinal nematodes in vitro and after passage through the gastrointestinal tract of sheep.

Semifield Evaluation of Improved Passive Outdoor Host Seeking Device (POHD) for Outdoor Control of Anopheles arabiensis Mosquitoes.

Despite the considerable progress made so far, the effectiveness and mass application of odour-baited outdoor mosquito control devices in pipelines is limited by several factors. These include the design and size of the devices, optimal placement of attractive blends, and nature of materials into which the blends are impregnated. The primary aim of this study was to manipulate these factors to improve the attractiveness of our recently developed passive outdoor host seeking device (POHD) to outdoor biting Anopheles arabiensis. Specifically, the study aimed to determine optimal placement of odour blends and killing bioactives in POHD for maximum attraction and killing of An. arabiensis and to assess the effects of blend types, formulation, and residual activity on attractiveness of the POHD to An. arabiensis. The POHDs baited with attractive blends, carbon dioxide (CO2), and bendiocarb-treated electrostatic netting were placed either towards the top or bottom openings, and other modifications were exposed to An. arabiensis under the semifield system at Ifakara Health Institute (IHI). Each night, a total of 100 starved female, 3–7-day-old, semifield reared An. arabiensis mosquitoes were released, collected the next morning (alive or dead), counted, and recorded. Live mosquitoes were maintained in the semifield insectary and monitored for 24 hours mortality. Each treatment combination of the POHD was tested in three replicates. Overall, the results indicated that the proportion of mosquitoes attracted to and killed in the POHD varied with position of attractants and killing agent (bendiocarb). The POHD with bottom placed attractants and bendiocarb attracted and killed higher proportion of mosquitoes compared to the POHD with top placed attractants and bendiocarb. The highest mortalities were observed when the POHD was baited with a combination of attractive blends and CO2. Moreover, the residual activity of attractive blends applied inside POHD varied with type and formulation of attractive blend. The POHD packed with Mbita and Ifakara blend in microencapsulated pellets (granules) attracted higher proportion of mosquitoes than that baited with soaked nylon-strip formulation of either blends. Interestingly, POHD baited with Mbita blend in microencapsulated pellets (granules) formulation attracted and killed higher proportion of mosquitoes (>90%) than that baited with Ifakara blend even 9 months after application. Conclusively, the POHD remained effective for a relatively longer period of time when baited with bottom placed synthetic blends and CO2 combination, thus warranting further trials under real life situations.

AN OUTLINE OF VARIABLES IN PELLETIZATION BY EXTRUSION AND SPHERONIZATION

Pelletization is an agglomeration process which converts fine granules or powders of bulk drugs into small, free-flowing, spherical units, known as pellets. The pelletization can be achieved either through agitation, compaction (extrusion-spheronization), drug layering and globulation. Among the various pelletization techniques extrusion–spheronization process is preferred over other methods for the preparation of pellets as it allows the incorporation of the higher amount of drug, modified physical characteristics of the drug (density, sphericity, narrow size distribution, smoother surface) and multiple drugs can be easily combined in the same unit. This current review summarizes the findings or investigations by the researchers on various variables, including process parameters, equipment parameters and formulation parameters influencing the quality of pellets. The article also focuses on process optimization and additives used in pellets formulation. To prepare the current review search criterion used was the parameters affecting final pellet characterization in the extrusion spheronization process. The sources were peer-reviewed relevant scientific articles of recognized journals. Keywords used as filters were extrusion, spheronization, formulation parameters, process parameters, equipment parameters, moisture content, granulating liquid, drying rate, extrusion temperature, spheronizer load, pelletization. Literature survey has been done in a range of years (1992-2019) regarding the various variables of the extrusion spheronization process, which affects and has foremost impact on the final quality of pellets so as to make the review updated and comprehensive.

Influence of the porosity of cushioning excipients on the compaction of coated multi-particulates

The compaction of multiple unit-pellet system (MUPS) tablets poses considerable challenges due to potential compaction-induced damage to the functional polymer coat and segregation of pellets from other excipients during the tableting process. This study was designed to investigate the impact of porous pellets as cushioning agent without issues related to segregation while tableting. Different drying techniques were applied to produce microcrystalline cellulose (MCC) pellets with various porosities. Sodium chloride was also added to the pellet formulation as a pore forming agent to generate a porous skeleton after production and aqueous extraction. The pellets fabricated were characterized for their porosity, crushing strength and yield pressure. Tablets were prepared using unlubricated pellets and their tensile strengths determined. Blends containing polymer-coated pellets and cushioning pellets of various porosities were compacted at different compaction pressures. The porous pellets exhibiting the best cushioning effect were used for MUPS tableting at different compression speeds with both gravity and force feeders. The findings from this study showed that pellet porosity was highest when drying was carried out in a freeze dryer, followed by fluid bed and least porous from the oven. There was an inverse relationship between pellet porosity and strength. The protective effect of cushioning pellets was mainly dependent on their porosity. The porosity of pellets manufactured by leaching NaCl from MCC-NaCl (1:1) pellets were 2.14-, 2.57- and 4.88-fold higher than that of MCC PH101 only pellets for oven, fluid bed and freeze dried pellets, respectively. Although the porosity of MCC PH101-NaCl (1:3) pellets was highest, they exhibited less cushioning effect than MCC PH101-NaCl (1:1). It was inferred that a good balance between porosity and bulk density of cushioning pellets was essential to be effective at protecting the coated pellets from damage during compaction. Compared with MUPS tablets prepared using unprocessed MCC PH105, the tablets prepared with the porous freeze dried MCC PH101 (NaCl fraction leached) pellets had improved drug content uniformity and were mechanically stronger.

FORMULATION AND EVALUATION OF FLOATING PELLETS OF OMEPRAZOLE BY EXTRUSION SPHERONIZATION METHOD

Objective: The aim of the present study was design, develop and to evaluate a model of floating sustained release pellets formulations for Omeprazole by extrusion and spheronization technique.&#x0D; Methods: Omeprazole at different drug to polymer ratios were prepared by extrusion and spheronization technique and the release rate of the drug from the pellets was studied. Further, the in-vitro release studies of pellets were carried out in 0.1N HCL for 12 hours. Prepared pellets were subjected to characterization by different techniques such as loose bulk density, tapped bulk density, compressibility index and angle of repose. To optimize the formulation on the basis of acceptable pellet properties friability, drug content, moisture content, and loss on drying and in-vitro drug release tests were done. In addition, the compatibility studies were performed by using FTIR and DSC.&#x0D; Results: These above studies indicated that the drug release can be modulated by varying the concentration of the polymer. The resulting formulation produced robust pellets with acceptable drug content and low friability. Further, release data was fitted to various mathematical models such as, Higuchi, Korsmeyer-Peppas, First-order, and Zero-order to evaluate the kinetics and mechanism of the drug release. Kinetic modeling of in-vitro dissolution profiles revealed the release mechanism ranges from Quasi-Fickian transport to Anomalous (non-Fickian transport), which was only dependent on the type and amount of polymer used. The drug release of the optimized formulation (F5) follows Zero order kinetics and the mechanism was found to be diffusion controlled. The FTIR and DSC studies reveal that there is no interaction between the drug and the polymer/excipients mixture.&#x0D; Keywords: Floating, Ethyl cellulose, HPMC, Pellets, Omeprazole.

Design of a Drug-Eluting Subcutaneous Implant of the Antiretroviral Tenofovir Alafenamide Fumarate

PurposeSexual transmission of HIV has been clinically proven to be preventable with a once-daily oral tablet; however, missed doses dramatically increase the risk of HIV infection. Long-acting subcutaneous implants do not allow the user to miss a dose. A desirable long-acting drug-eluting implant can deliver a constant amount of drug, adjust the delivered dose, and be readily manufactured. We present a long-acting, subcutaneous implant design composed of tenofovir alafenamide hemifumarate (TAF) pellets loaded in a sealed polyether urethane tube for the prevention of HIV transmission.MethodsImplants were prepared with pressed drug pellets and extruded polyurethane tubing. In vitro release rate of implants using different pellet formulations, rate-controlling membranes, and geometries were measured.ResultsTenofovir alafenamide release appeared to be governed by a pseudo-steady state and followed a mass transport model of release from a cylindrical drug reservoir. Implant seal integrity was tested and confirmed using mechanical testing. The inclusion of sodium chloride in the pellet increased the release rate and reduced initial lag. The release was sustained for 100 days.ConclusionsThe release rate of tenofovir alafenamide mechanistically varied with geometry and rate controlling membrane composition. The polyether urethane implant presented herein is modular and tunable to adjust the release rate and duration of the TAF release.

Administration of an Orally Delivered Substrate Targeting a Mammalian Zoonotic Pathogen Reservoir Population: Novel Application and Biomarker Analysis.

Reservoir-targeted vaccines (RTVs) have the potential to be effective at breaking the transmission cycle of many tick-borne pathogens including, but not limited to, Borrelia burgdorferi, B. miyamotoi, B. mayonii, Babesia microti, and Anaplasma phagocytophilum. To determine what proportion of a wild reservoir species we could effectively target, we distributed an experimental non-RTV Rhodamine B (RhB)-coated pellet formulation devoid of nutrient supplementation using bait boxes with ad libitum access, in battery-operated time-release bait stations, and by hand broadcast. Regardless of distribution method, a total of 208 of 242 (86%) white-footed mouse (Peromyscus leucopus) captures were positive for RhB by either pelage staining or by detecting fluorescent expression in vibrissae under a microscope. In bait box locations, 91% of captured mice were RhB-positive, 89% in hand broadcast locations, and 80% in time-release station locations. Based on results, we are confident that the bait formulation was readily accepted regardless of distribution technique, reached a substantial proportion of the reservoir population, and provides an effective vehicle to deliver a range of RTVs to targeted, wild, pathogen reservoir populations.

Development of Multiparticulate Oral Dosage Form of Zopiclone

The aim of the present study is to develop and evaluate immediate release zopiclone pellets by using the extrusion-spheronization technique for treatment of insomnia. Immediate release pellets of zopiclone were prepared by using sodium starch glycolate (SSG) and HPMC E-5 as disintegrant and binder respectively along with microcrystalline cellulose (MCC) as a spheronizing aid, corn starch and lactose (monohydrate)as fillers. Pellet formulation was further optimized for disintegration time and percent drug release after 45 min. using 32 factorial design. There was no interaction between drug and polymer by FT-IR study. The zopiclone pellets batch (F7) prepared with SSG (4%) and HPMC E-5 (2%) spheronized at 850 RPM was found to be optimized. The optimized batch showed narrow particle size, less disintegration time and immediate drug release of 94.8% after 45 min. For treatment of insomnia, immediate release zopiclone pellets formulated in this study, can serve as an alternative to tablet dosage form.