Effect Of Formulation Parameters Research Articles

Effect of Formulation Parameters and Physiological Environment on Amlodipine Release Kinetics Encapsulated in Biodegradable Polymers and Optimized by Design Methodology

Effect of Formulation Parameters and Physiological Environment on Amlodipine Release Kinetics Encapsulated in Biodegradable Polymers and Optimized by Design Methodology

Effects of food formulation on bioavailability of phytosterols: phytosterol structures, delivery carriers, and food matrices.

Daily intake of phytosterols (PSs) as a diet supplement can lower blood-cholesterol levels and reduce the risks of cardiovascular diseases. However, the high crystallinity, low water solubility, easy oxidizability, and other characteristics of PSs restrict their application and bioavailability in food products. The formulation parameters including the structures of PSs, delivery carriers, and food matrices may play an important role in the release, dissolution, transport, and absorption of PSs in functional foods. In this paper, the effects of formulation parameters, including phytosterol structures, delivery carriers, and food matrices, on the bioavailability of phytosterols are summarized and suggestions are provided for the formulation design of functional foods. The side chain and hydroxyl esterification group of PSs may significantly affect their lipid or water solubilities and micellization capacities, which in turn affect the bioavailability of PSs. Selecting suitable delivery carriers based on the characteristics of the food system can reduce the crystallinity and oxidation of PSs and control the release of PSs, thereby improving the PS stability and delivery efficiency. Moreover, the ingredients of the carriers or food products would also influence the release, solubility, transport, and absorption of PSs in the gastrointestinal tract (GIT).

Preparation of chitosan nanoparticles by ionotropic gelation technique: Effects of formulation parameters and in vitro characterization

Chitosan (CS) nanoparticles (NPs) prepared by ionotropic gelation technique are one of the forcefully studied nanosystems used for drug delivery. Though, a deficiency of inter-laboratory reproducibility and a poor physicochemical understanding of particle formation process have been decelerating their potential market applications. To report these shortcomings, the current work offerings the effect of primary formulation parameters on CSNPs formation by a single factor test. The stability of CSNPs at various pH and ionic strength was also analyzed. The mean particle size, zeta potential (ZP), and polydispersity index (PDI) of optimum CSNPs were 67.60±0.11 nm, +33.23±1.20 mV and 0.26±0.00, respectively. The SEM and TEM studies proved that the CSNPs were well dispersed spherical shape with good particle size distributions. The FTIR spectrum indicated that cross-linking was successfully carried out. To sum up, we found that by controlling the formulations parameters, it is possible to control in a reproducible manner the production and characteristics of CSNPs in the range of nanomaterial size.

Nanosuspensions of Selexipag: Formulation, Characterization, and in vitro Evaluation

Selexipag is an orally selective long-acting prostacyclin receptor agonist, which indicated for the treatment of pulmonary arterial hypertension. It is practically insoluble in water ( class II, according to BCS). This work aims to prepare and optimized Selexipag nanosuspensions to achieve an enhancement in the in vitro dissolution rate. The solvent antisolvent precipitation method was used for the production of nanosuspension, and the effect of formulation parameters (stabilizer type, drug: stabilizer ratio, and use of co-stabilizer) and process parameter (stirring speed) on the particle size and polydispersity index were studied. SLPNS prepared with Soluplus® as amain stabilizer (F15) showed the smallest particle size 47nm with PDI and Zeta potential value of 0.073 and -47mV, respectively. SLPNS exhibited an increase in the dissolution rate in phosphate buffer pH 6.8 (100% drug release during 60 min) compared to the pure drug ( 40% during the same time). This result indicates that SLPNS is an efficient way of improving the dissolution rate.

Preparation of Nano‐Emulsion‐Based Hydrogels Conjugated Curcumin as Model Functional Lipid Bioactive Compound

AbstractThe preparation of nanoemulsion‐based alginate hydrogels, containing curcumin was the aim of current study. The nanoemulsions of coconut oil were prepared using solvent‐displacement technique and then the obtained nanoemulsions were converted to hydrogels using the ion‐gelling process. The effects of formulation parameters, namely, sodium alginate concentration (1–2 g L−1), the weight ratio of calcium chloride to sodium alginate (2–4), and curcumin to sodium alginate (1–3), were also evaluated on swelling percentage, gel fraction, curcumin load, curcumin release, and antibacterial inhibitory zone of hydrogels. All studied characteristics were successfully correlated to the selected independent variables by second‐order polynomial equations as models, with relatively high coefficients of determinations (R2 > 86). According to multiple numerical optimization analysis, the most desired hydrogels can be obtained using 1.9 g L−1 sodium alginate, curcumin/sodium alginate of 2.5 g g−1, and calcium chloride/sodium alginate of 2.2 g g−1, with the maximum swelling ratio (216%), gel fraction (29.9%), curcumin load (59.12%), antibacterial activity (clear‐zone diameter of 5.27 cm), and the least curcumin release after 12 hours (87.75%). It was also resulted that the curcumin release from prepared optimum hydrogel obeys the first order kinetics. No significant differences between the measured and predicted data confirmed the suitability of suggested models.

Losartan potassium sustained release pellets with improved in vitro and in vivo performance

The aim of this study was to formulate and evaluate SR matrix pellets containing losartan potassium (LP) solid dispersion using extrusion–spheronization technique to minimize the fluctuation of its plasma concentration. LP solid dispersions were prepared by using different hydrophobic polymers at different weight ratios (0.5, 1, 2, and 5%). LP-Eudragit RS solid dispersion at 1:5 ratio resulted in slower drug release (only 20% of LP was released in about 8 h). Different concentrations of hydrophilic polymer, PEG 6000, were mixed with Avicel® PH 101 to prepare the LP SR matrix pellets containing solid dispersion using 32 full factorial design to evaluate the effects of formulation parameters on the pellets attributes. The magnitude of torque for the pellet wet masses and binder ratio were decreased significantly with increasing PEG 6000 concentration. LP sustained release pellet formula composed of 9.24% PEG 6000 and 8 × 10−9% PVP K30 solution was chosen as optimized formula. Pharmacokinetic studies revealed that calculated t max was 9.72 ± 2.22 h from the optimized sustained release pellets compared to 2.11 ± 0.49 h in case of Cozaar® immediate release tablet, indicating a slower release of the LP from pellets.

PLGA nanoparticle preparations by emulsification and nanoprecipitation techniques: effects of formulation parameters.

This study presents the influence of the primary formulation parameters on the formation of poly-dl-lactic-co-glycolic nanoparticles by the emulsification-solvent evaporation, and the nanoprecipitation techniques. In the emulsification-solvent evaporation technique, the polymer and tensoactive concentrations, the organic solvent fraction, and the sonication amplitude effects were analyzed. Similarly, in the nanoprecipitation technique the polymer and tensoactive concentrations, the organic solvent fraction and the injection speed were varied. Additionally, the agitation speed during solvent evaporation, the centrifugation speeds and the use of cryoprotectants in the freeze-drying process were analyzed. Nanoparticles were characterized by dynamic light scattering, laser Doppler electrophoresis, and scanning electron microscopy, and the results were evaluated by statistical analysis. Nanoparticle physicochemical characteristics can be adjusted by varying the formulation parameters to obtain specific sizes and stable nanoparticles. Also, by adjusting these parameters, the nanoparticle preparation processes have the potential to be tuned to yield nanoparticles with specific characteristics while maintaining reproducible results.

EFFECT OF DIFFERENT FORMULATION VARIABLES ON RELEASE CHARACTERISTICS OF GASTRO-FLOATING MICROSPHERES OF ETHYL CELLULOSE/CARBOPOL 934P ENCAPSULATING SORAFENIB

Objective: The aim of this study is to prepare floating hollow microspheres encapsulating Sorafenib (SFN) to enhance its oral bioavailability. 
 Methods: Gastro-floating hollow adhesive microspheres containing SFN were produced by using an emulsion solvent evaporation technique with ether and ethanol as solvents. Ethyl cellulose and carbopol 934P were used as the encapsulating carriers. The effects of formulation parameters like, solvent volume ratio, and drug to polymer ratio (D: P ratio), encapsulation efficiency percentage EE%, floating percentage, and release of SFN after 12 h (Rel12) were investigated and analyzed using a (32) full factorial design.
 Results: The floating percentage of the microspheres was found to be 76.5%. The in vitro drug release from these hollow microspheres followed the Higuchi model equation. The in vivo results showed that approximately 1.96-fold improvement in the relative bioavailability of the microspheres compared with that of the commercial tablet. 
 Conclusion: The results demonstrate that the hollow microspheres with good gastro-floating ability are a promising delivery system to enhance SFN bioavailability.

Fabrication of Novel Hierarchical Multicompartment Highly Stable Triple Emulsions for the Segregation and Protection of Multiple Cargos by Spatial Co-encapsulation

High-order multiple emulsions are of great interest in both fundamental research and industrial applications as vehicles for their encapsulation capability of actives. In this work, we report a hierarchically multicompartmental highly stable triple emulsion by emulsifying and assembling of natural Quillaja saponin. Water-in-oil-in-(oil-in-water) (W2/O2/(O1/W1)) triple emulsion indicates that the compartmented system consisted of surfaced saponin-coated nanodroplets (SNDs) and dispersed oil globules, which in turn contained smaller aqueous droplets. The effects of formulation parameters, including lipophilic emulsifier content, oil fraction, and SND concentration, on the formation of multiple emulsions were systematically investigated. The assembly into fibrillar network of SNDs at the outer oil-water interface effectively protected the triple emulsion droplets against flocculation and coalescence, and strongly prevented the osmotic-driven water diffusion between the internal water droplets and the external water phase, thus contributing to superior stability during 180 days storage. All of these characteristics make the multicompartmentalized emulsions suitable to co-encapsulate a hydrophilic bioactive (gardenia blue) and two hydrophobic bioactives (eapsanthin and curcumin) in a single emulsion droplet hierarchically for the segregation and protection of multiple cargos. This approach offers a promising route toward accessing the next generation of functional deliveries and encapsulation strategies.

Effect of formulation parameters on pharmacokinetics, pharmacodynamics, and safety of diclofenac nanomedicine.

This study reports the development of a nanoformulation of diclofenac sodium, a potent non-steroidal anti-inflammatory drug, at its clinical dose, utilizing a FDA approved polymer, hydroxyethyl starch. The study specifically focused on the control of pharmacokinetics, pharmacodynamics, and biodistribution by particle surface functionalization and alteration of excipient levels in the final formulation. Stable diclofenac sodium-loaded hydroxyethyl starch nanoparticles (nanodiclo) of size 170 ± 5nm and entrapment efficiency 72 ± 3% were prepared. Free diclofenac, nanodiclo, nanodiclo surface functionalized by PEGylation, nanodiclo with excipients removed, and finally PEGylated nanodiclo with excipients removed were all tested comparatively at two different doses. The results showed substantial impact of both excipients and PEGylation on the pharmacokinetics and pharmacodynamics in vivo. Further, the results proved that excipient removed PEGylated nanodiclo at lower dose achieved clinical therapeutic levels in blood for up to 120h, with minimal accumulation in critical organs, and much better efficacy than other controls.

Floating drug delivery system of itraconazole: Formulation, in vitro and in vivo studies

A multiple unit oral floating drug delivery system of itraconazole was developed to prolong gastric residence time, target stomach mucosa and increase drug bioavailability. To prepare non-effervescent floating microspheres/beads, ionotropic gelation method was used. Since the solubility of itraconazole is low at pH 1.2, it was attempted to increase the solubility by preparing inclusion complexes using randomly methylated beta-cyclodextrin and with polyvinylpyrrolidone cross linked and starch. In this study, the effects of formulation parameters like, concentration and types of polymer, crosslinking agent and the excipients, the floating ability, surface characteristics and drug release profiles were investigated. Optimum formulation (NG17) was used for Caco-2 cell culture studies. In permeability studies, at pH 5, 6 and 7.4, the formulation NG17 at pH 5, which is the pH of the proximal region of small intestine (absorption window of itraconazole), showed the highest permeability value which is 5.88 × 10−6 cm/s. NG17 was also used for in vivo imaging studies. It was conducted in rabbits by using gamma scintigraphy and obtained that NG17 floated for 6.5 h in the stomach. As a result, it was found that, with non-effervescent floating bead formulations, the bioavailability of itraconazole can be improved.

EFFECTS OF FORMULATION PARAMETERS ON PROPERTIES OF GASTRIC FLOATING TABLETS CONTAINING POORLY SOLUBLE DRUG: DICLOFENAC SODIUM

Objective: The objective of this study was to prepare and investigate the effects of formulation parameters on the properties of gastric floating tablets containing diclofenac sodium (DICL) as a model of poorly soluble acidic drug, sodium bicarbonate (NaHCO3) or calcium carbonate (CaCO3) as gas-forming agent, hydroxypropyl methylcellulose (HPMC) K100M or K15M as swelling polymer and sodium lauryl sulfate (SLS) as wetting agent.Methods: DICL floating tablets were prepared using direct compression method. The compressed tablets were evaluated for tablet properties, swelling index, and in vitro buoyancy. The in vitro release under non-sink condition was determined. Molecular interaction was studied using differential scanning calorimetry and fourier transform infrared spectroscopy.Results: The tablet properties of all DICL floating tablets were within the acceptance criteria. The molecular interaction between DICL and excipients in the formulation was excluded. Depends on the formulation compositions, the swelling index at 3 h (SI) ranged from 44±11 to 1158±33 %, whereas the buoyancy properties namely floating lag time (FLT) and total floating time (TFT) were 0.33±0.03 to 10.04±0.04 min and 10.0±0.0 to>12 h, respectively. NaHCO3 showed higher swelling, buoyancy and release properties compared to those of CaCO3. NaHCO3 at 20% gave sufficient swelling (SI of 1074±16 %), buoyancy (FLT of 0.39±0.03 min, TFT of>12 h) and release properties (cumulative release of 5.83±0.02 %). HPMC K100M showed better swelling property of which its initial swelling rate was 1412±25 %/h compared to HPMC K15M (1042±31 %/h). HPMC K100M at 20% showed better buoyancy and release properties compared to those obtained from HPMC K100M at 30%. The release testing under non-sink conditions was able to distinguish the effect of formulation parameters on the DICL release profiles. Incorporation of SLS at 0.25% could enhance both release rate and cumulative release of DICL from the floating tablets. Nevertheless, it showed the unacceptable adverse effect on swelling and buoyancy properties of DICL floating tablets. The TFT of DICL floating tablets containing 0.25% SLS was only 0.5±0.0 h.Conclusion: DICL floating tablets were successfully prepared. Tablets possessing suitable swelling and buoyancy properties were obtained using NaHCO3 at 20% as a gas-forming agent, with HPMC K100M at 10 and 20% as floating matrix and swelling polymer. Addition of SLS as wetting and solubilizing agent showed the unacceptable adverse effect on the swelling and buoyancy properties of DICL floating tablets. The release under sink conditions and/or in vivo pharmacokinetic studies shall be further performed.

Preparation and characterization of nanoemulsion based β-carotene hydrogels.

The aim of this study was to develop β-carotene hydrogels using nanoemulsions, with increased β-carotene aqueous solubility, bioavailability and improved physical and chemical stabilities. The nanoemulsion of β-carotene was prepared using a solvent-displacement technique and converted into hydrogels using sodium alginate as stabilizer and calcium chloride as cross-linker. The effects of formulation parameters, mainly, the effects sodium alginate and calcium chloride concentrations on the physicochemical properties of hydrogels were evaluated using a surface response methodology. The second order polynomial equations, subsequently, were suggested to predict the changes of studied physicochemical characteristics of hydrogels, with relatively high regression of coefficients values. Based on numerical multiple optimization, it was concluded that using 4.1g/l sodium alginate and 5.7g/l calcium chloride, resulted in a hydrogel with the most desired physicochemical characteristics. No significant differences between the measured and predicted data, reconfirmed the accuracy of the models.

Vasorelaxant effect of standardized extract of Cecropia glaziovii Snethl encapsulated in PLGA microparticles: In vitro activity, formulation development and release studies

In this study, the standardized dry extract of C. glaziovii (SDE) provided a significant vasorelaxant effect after contractions induced by phenylephrine in rat aortic rings in an endothelium-dependent manner, confirming that endothelial factors are needed to stimulate this response. A vasorelaxation close to that of acetylcholine was achieved, justifying the development of new formulations for this plant material. In this context, microparticles were selected to encapsulate SDE and the double emulsion technique was considered because of the hydrophilic nature of plant material. Two experimental designs were applied. Firstly, the effect of formulation parameters on particle size, size distribution and encapsulation efficiency (EE) was evaluated. As low EE was achieved, the effect of the osmotic pressure of the external phase was evaluated in a second experimental design. The presence of the osmotic agent (NaCl) impacted positively on the EE and slower in vitro release profile was obtained, which is desired in controlled release systems. The formation of denser and less porous particle surface, which was identified by SEM analysis, contributes to explain these findings. Microstructures showed to be a promising delivery system for the C. glaziovii SDE considering that a sustained release was achieved.

Microextraction techniques in antibiotic monitoring in body fluids: Recent trends and future

ABSTRACTThe analysis of drugs in biomedical discipline targets a broad range of aims such as therapeutic drug monitoring, pharmacokinetic study to investigate the drug bioavailability, bioequivalence tests to evaluate the effect of formulation parameters, toxicology, and forensic science. Because of the low levels of typical antibiotics in plasma, blood, urine, exhalation samples, and other biological fluids as well as complex matrix of biological media, adequate sample preparation methods should be implemented for quantification of antibiotics. In this review, developments in well-established microextraction techniques for the clinical analysis of biological samples will be reviewed and discussed. This article presents an overview of microextraction methods for biological samples, focusing especially on antibiotics.

Preparation of TPP-crosslinked chitosan microparticles by spray drying for the controlled delivery of progesterone intended for estrus synchronization in cattle.

Planned reproduction in cattle involves regulation of estrous cycle and the use of artificial insemination. Cycle control includes the administration of exogenous progesterone during 5-8days in a controlled manner allowing females to synchronize their ovulation. Several progesterone delivery systems are commercially available but they have several drawbacks. The aim of the present contribution was to evaluate chitosan microparticles entrapping progesterone as an alternative system. Microparticles were prepared by spray drying. The effect of formulation parameters and experimental conditions on particle features and delivery was studied. A mathematical model to predict progesterone plasma concentration in animals was developed and validated with experimental data. Microparticle size was not affected by formulation parameters but sphericity enhances as Tween 80 content increases and it impairs as TPP content rises. Z potential decreases as phosphate content rises. Particles remain stable in acidic solution but the addition of surfactant is required to stabilize dispersions in neutral medium. Encapsulation efficiencies was 69-75%. In vitro delivery studies showed burst and diffusion-controlled phases, being progesterone released faster at low pH. In addition, delivery extend in cows was affected mainly by particle size and hormone initial content, while the amount injected altered plasma concentration. Theoretical predictions with excellent accuracy were obtained. The mathematical model developed can help to find proper particle features to reach specific delivery rates in the animals. This not only save time, money and effort but also minimized experimentation with animals which is desired from an ethical point of view.

Effects of Formulation Parameters and Process Variables on the Properties of Granules Obtained by Reactive Granulation

In this work, granulation between dodecyl-benzenesulfonic acid and sodium carbonate was investigated in a laboratory-scale high shear mixer. The effects of formulation parameters and process variables, including primary carbonate size, binder content, impeller speed, and operating temperature, were correlated to the properties of the product granules. Design of experiment and analysis of variance were combined to analyze the experimental data, and results showed that larger granule sizes with fewer fine particles can be obtained by employing higher binder contents and larger sodium carbonate sizes. The shear force of the impeller can extensively break oversized granules. The binder content exerted a contrasting effect on the flowability of granules formed with two kinds of sodium carbonate, likely because of differences in the liquid saturation of the solids. The dissolution rate determined by in-line size analysis showed that high binder contents were beneficial to dissolution performance, and the relationships between Hunter color and tested parameters were evaluated. The results of this work can be used as a reliable guidance for process control and optimization in powder detergent manufacturing.

Liquisolid Technique: An Approach to Enhance the Dissolution Rate of Olanzapine

The present work was aimed at enhancing the dissolution rate of olanzapine, an antipsychotic agent using the liquisolid technique. Liquisolid system is an innovative technique used for enhancing dissolution rate and bioavailability of poorly soluble drugs. A mathematical model was utilized to formulate liquisolid tablets. Two non-volatile liquids were used in the design of liquisolid tablets, Tween 80 and propylene glycol. The effect of formulation parameters, such as drug:non-volatile liquid ratio and carrier:coating ratio were observed. Microcrystalline cellulose and silica were used as carrier and coating materials, respectively. All liquisolid formulations showed higher drug dissolution rate than directly compressible tablets and marketed tablets. Differential scanning calorimetry revealed that the drug has got solubilised in the liquid vehicle which was further supported by x-ray diffraction studies and scanning electron microscopy. Infrared spectroscopy studies indicated the absence of incompatibility between drug and non-volatile solvents. This study shows that liquisolid technique is a promising alternative for improvement of dissolution rate of water insoluble drug.

Preparation and characterization of bioactive oils nanoemulsions: Effect of oil unsaturation degree, emulsifier type and concentration

ABSTRACTThe effect of formulation parameters namely oil type, emulsifier type and concentration was assessed on various properties of the nanoemulsions. All nanoemulsions yielded droplets with a desirable size ranged from 38.5 to 127.9 nm. The findings showed that emulsifier type had significant effects on the physicochemical properties of emulsions. Emulsifier concentration had a negative correlation with droplet diameter, turbidity and positive correlation with polydispersity index, viscosity and creaming stability. Nanoemulsions prepared from pomegranate seed oil were different from that of two other oils in droplet size, viscosity, creaming and turbidity because of its higher intrinsic viscosity and degree of unsaturation.

Nanoethosomal formulation of gammaoryzanol for skin-aging protection and wrinkle improvement: a histopathological study

Background: Free radical scavengers and antioxidants, with the main focus on enhanced targeting to the skin layers, can provide protection against skin ageing.Objective: The aim of the present study was to prepare nanoethosomal formulation of gammaoryzanol (GO), a water insoluble antioxidant, for its dermal delivery to prevent skin aging.Methods: Nanoethosomal formulation was prepared by a modified ethanol injection method and characterized by using laser light scattering, scanning electronic microscope (SEM) and X-ray diffraction (XRD) techniques. The effects of formulation parameters on nanoparticle size, encapsulation efficiency percent (EE%) and loading capacity percent (LC%) were investigated. Antioxidant activity of GO-loaded formulation was investigated in vitro using normal African green monkey kidney fibroblast cells (Vero). The effect of control and GO-loaded nanoethosomal formulation on superoxide dismutase (SOD) and malondialdehyde (MDA) content of rat skin was also probed. Furthermore, the effect of GO-loaded nanoethosomes on skin wrinkle improvement was studied by dermoscopic and histological examination on healthy humans and UV-irradiated rats, respectively.Results: The optimized nanoethosomal formulation showed promising characteristics including narrow size distribution 0.17 ± 0.02, mean diameter of 98.9 ± 0.05 nm, EE% of 97.12 ± 3.62%, LC% of 13.87 ± 1.36% and zeta potential value of –15.1 ± 0.9 mV. The XRD results confirmed uniform drug dispersion in the nanoethosomes structure. In vitro and in vivo antioxidant studies confirmed the superior antioxidant effect of GO-loaded nanoethosomal formulation compared with control groups (blank nanoethosomes and GO suspension).Conclusions: Nanoethosomes was a promising carrier for dermal delivery of GO and consequently had superior anti-aging effect.