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Content uniformity (CU) is a crucial evaluation factor, especially for low-dose oral formulations. Spray-dried monohydrate lactose is generally recommended for direct compression/dry granulation, but we observed that it showed advantages in the wet granulation tableting method for low-dose tablet formulation. In this study, several commercial brand...
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The study deals with the effects of hydrophilicity and hydrophobicity of three commonly used diluents
on IR tablets of model soluble and insoluble drugs. Conventional tablets with diluents, used individually and in combinations, were prepared by direct compression, dry granulation and wet granulation. Effects of binder
amount, disintegrant and its...
The objective of the present study was to develop bi-layer tablets of lornoxicam, a highly potent nonsteroidal antiinflammatory drug with short half-life, that are characterized by initial burst drug release in the stomach and comply with the release requirements of sustained-release products. Each of the proposed bi-layer tablets is composed of an...
Citations
... In vitro release data (untransformed) was utilized to determine the release kinetics of DTX. Various mathematical models used in describing drug release are zero-order kinetics, Higuchi model, first-order kinetics, Hixon-Crowell model, and Korsmeyer-Peppas model with its power equation to provide with 'n' the diffusion coefficient [47]. Dissolution data modelling was utilized from DD solver excel add ins to analyze the drug release for adjusted R 2 , AIC-Akaike Information Criterion, MSC Model selection criteria, and 'n' diffusion exponent for selection of mechanism of release followed. ...
Background
Millions of individuals worldwide are affected by cancer, with increasing instances by 1% annually and strikingly high mortality rates of 0.4% per year for cancers of the oral cavity and 2% for cancers of the tongue, tonsil, and oropharynx. Here we propose the administration of the water-insoluble anti-cancer drug docetaxel (DTX) along with an adjuvant C6 ceramide (Cer) through the buccal route to overcome the challenges such as the wet site of administration and inadequate availability of the drug on-site, by increasing the residence time of the mucoadhesive film through the selection of polymers.Materials and Method
Mucoadhesive films were prepared by solvent casting method. Using chitosan, HPMC K4M, HEC, and PVA homo- and heteroblended films (P1–P8) were prepared and optimized for the selection of suitable polymer composition. As a pre-formulation investigation, drug-excipient compatibilities (DSC and ATR-FTIR) were carried out. The DSC and ATR-FTIR investigation showed that the drug and the polymers had excellent compatibility. The films prepared were characterized for their percentage swelling index, residence time, physical appearance, weight, thickness, surface pH, folding endurance FE, percentage moisture absorption PMa, surface morphology SEM, drug content uniformity, in vitro drug release, and in vitro MTT assay. Results.On the basis of the results of percentage swelling index, residence time, and dissolution data modelling applied using DD solver excel Add-in, from homo- and heteroblends of polymers scrutinized, chitosan, HEC, and PVA were selected for the choice of polymers as docetaxel showed non-Fickian diffusional release from the erodible polymeric film. Chitosan, HEC, and PVA were optimized using Box-Behnken design with the help of Design-Expert® software. Three independent variables were considered: amount of chitosan (A), amount of HEC (B), and PVA concentration (C). The percentage swelling index (R1: SI%) and residence time (min) (R2: RT) were selected as dependent variables or responses. CHeP10 with percentage swelling index 40.3 ± 1.15, residence time 326.66 ± 3.05 min, and 60.00 ± 0.734% drug released in 6 h was chosen for in vitro cell line studies against the CaL-27 cell line, where DTX-Cer-loaded CHeP10 showed a 15-time reduction of IC50 of plain DTX from 1.743 to 0.1108 nM. On the basis of these studies, we may conclude that the current approach comprising polymeric films can be successfully used for the local and enhanced anti-cancer activity of docetaxel for oral cancer.
... As follow the Zero-order model, the rate of piperine release from the SD formulation prepared at the highest temperature of 125°C is independent of drug concentration and remains constant over time. Furthermore, the zero-order model of piperine may explain that the drug does not disaggregate from the dosage form, and the dissolution process is slow [38]. ...
... Granules from homogenously mixed formulations (Table 1) containing ibuprofen, spray dried lactose BP, Talc BP and the binders (2.5% w/w, 5.0% w/w, 7.5% w/w, and 10.0% w/w) were formed from each batch based on a previous design of experiment described in the literature [14]. W. Huang et al. [15] reported the formulation of wet granules using spray-dried lactose, which resulted in products with good flowability and compressibility. For each batch, the weighed quantity of ibuprofen and either ENTA or CENTA (or gelatin BP) powders were premixed thoroughly in a Kenwood plenary mixer (United Kingdom, KVL65.001WH), this was followed by the addition of the weighed quantity of talc and spray dried lactose BP until a homogenous mixture was achieved. ...
The incorporation of modified polymers in drug formulations is primarily due to their low toxicity, affordability, availability, compatibility with biological membranes, economic feasibility and bio-degradability.This study investigated the compressional and release characteristics of ibuprofen tablet formulations containing natural and modified Entandophragma angolense gum. Entandophragma angolense gum (ENTA) was extracted and modified by carboxymethylation to yield CENTA. Ibuprofen tablets containing varying binder concentrations (2.5-10% w/w) of ENTA and CENTA (compared with gelatin BP) were formulated by wet granulation. Crushing strength (CS) and friability (FR) were used in assessing the mechanical properties of the tablets, while disintegration and dissolution times accounted for drug release parameters. Density measurements, Kawakita equations and Heckel plots were used to assess the compressional properties of the formulations. The results were analysed using ANOVA at ɑ0.05. Generally, there was a direct relationship between the concentration of the polymers and the CS of the tablets, while an inverse relationship was observed for FR. The CS ranked ENTA > CENTA > gelatin BP. Carboxymethylation of ENTA enhanced drug release (t30% and t80%). Formulations containing CENTA had a slower and faster onset of plastic deformation; mean yield pressure (Py), ranked ENTA > CENTA > gelatin BP. A measure of the rearrangement phase at the early stages of compression (DB) was highest for CENTA at all concentrations. CENTA compared favourably with gelatin BP and showed better mechanical and release characteristics than ENTA. Also, CENTA shows good potential as a binder in fast disintegrating ibuprofen tablets, especially when incorporated at low concentrations.
... Indirectly, it indicates the ability of powder particles to slide to the empty spaces in the powder mass via their linear translation, rotation or reorientation. The degree of flowability and compressibility pertaining to Hi and Ci are presented in Table 1 [31,13]. Particles with Ci value between 0 to 10 bears excellent compressibility. ...
The solid wastes produced by the industries are becoming an ever-alarming issue for the environment,
health and economy. The metal cutting industries and the coal-fired thermal power plants produce metal
chips and coal fly ash (CFA) in abundance. In contrast to traditional utilization and recycling, a new
approach is conceived to fabricate metal matrix composites (MMCs) through the powder metallurgy
(P/M) technique. For comparison, the commercial iron powder, CFA mixture with mild steel machining
chips (MSMCs) were studied for their rheological and compaction properties. The morphology and elemental characteristics of the starting materials were explored by scanning electron microscope (SEM) and energy dispersive spectroscopy (EDS). The influence of CFA on the flowability behaviour was exhibited through the Hausner ratio and the angle of repose. At the same time, the compressibility behaviour was evaluated by Carr’s index and linear compaction equations. During analysis, it was observed that the
addition of CFA to the iron powder and MSMCs enhanced their rheological behaviour significantly. It has been concluded that the CFA spherical particles with a high surface finish have acted as a lubricating medium among the irregular and non-spherical iron particles and MSMCs. Further, the inclusion of CFA (0–15 wt.%) reduced the green density up to significant levels, which might be helpful to improve the specific mechanical properties of the MMCs synthesized thereof. Also, the addition of CFA to the iron
powder and MSMCs reduced their ability to plastic deformation, which eventually improved the strengthening of the MMCs through the load transfer mechanism.
... This is an indicator of the ability of powder particles to move and occupy the free spaces through linear translation, rotation and reorientation. The extent of flowability corresponding to the values of the Hausner ratio and Carr's index are given in Table 1 [46]. Particles bearing excellent flowability possess Carr's index values between 0 to 10. ...
... As described previously, the shape of the powder particles is an important parameter influencing their rheology. Circularity or sphericity ( ) of particles can be calculated as (4× area)/perimeter 2 , where equals 1, indicating a perfect sphere [46]. ...
... Hausner ratio and Carr's index based flowability[46]. ...
In this article, a detailed mineralogical, micromeritics and rheological study of the materials such as Fe powder,
SiC powder, Al2O3 powder, WC powder, coal fly ash (CFA), mild steel turning chips (MSTCs), mild steel
grinding chips (MSGCs) and aluminium saw chips (ASCs) is presented. The elemental characterization of these
materials was carried out using Energy-dispersive X-ray spectroscopy (EDS). The morphology of these materials
was investigated using Field emission electron microscopy (FESEM). The particle size and their distribution
were evaluated by processing FESEM micrographs through ImageJ software. The apparent and tap densities
were estimated as per ASTM standards. The flowability of the materials was estimated through Hausner ratio,
Carr’s index and further validated by angle of repose. During the analysis of the characterization results, it
was perceived that the density and the morphology of the powder particles, particulates and steel chips have a
significant influence on their derived properties. However, the apparent density was found to have significant
influence on the angle of repose and flowability of the material under consideration. The spherical morphology
of the particulates rendered them with acceptable flowability. The sharp-edged and agglomerated particulates
resulted in a higher angle of repose and lower flowability. However, among the chips, MSGCs possess suitable
micromeritic and rheological characteristics, which make them suitable to be processed through powder
metallurgy techniques. Further, MSTCs and ASCs exhibited suitable rheological properties comparable with
the powder produced through traditional methods. The results demonstrate that the waste metallic chips can
be directly recycled through powder metallurgy, circumventing the time consumed in ball milling operation.
... This model describes a drug release rate which is independent of its concentration [6][7][8] . This type of dissolution usually happens in dosage forms that do not disaggregate, and it is usually slow 9 . Rate of drug release is usually constant and drug level in the blood remains constant throughout delivery 10 . ...
... Here the drug release rate is dependent on the drug of interest's concentration. It can be shown by the equation: In a situation whereby the drug concentration in the formulation is lower than its solubility, the release occurs through a porous system and it can be expressed thus: Some assumptions made are that; Drug solubility is lower than initial drug concentration, perfect sink conditions are achieved and maintained, drug diffusivity is constant, swelling of polymer is negligible 10 , diffusion occurs only in one dimension (edge effect negligible) 4,9,10 . ...
Awareness of the release kinetics of active drugs is important in formulating drugs that have the desired delivery and in predicting the behaviour of the formulated drug in vivo. The study aims to determine the mechanism of drug release from griseofulvin tablets formulated with different surfactants using mathematical models and to compare the use of graphs and DD solver software in fitting dissolution profiles to kinetic models. The batches P1 -P3 were composed of the surfactant - PEG 4000 in different concentrations. A control batch without surfactant and a commercial brand (Mycoxyl 500) were used for comparison. Granule and tablet quality tests indicated quality formulations. Dissolution profiles showed that the surfactant improved drug release of griseofulvin and batches (batches P1 -P3) formulated with PEG 4000 had the best release profiles comparable with the commercial brand. The Excel Add-in DD solver and kinetic plots were used to determine the kinetic model of best fit. The Higuchi model was the best fit for batches P1 -P3. The first order and Hixon -Crowell also fit batches P2 and P3. The Korsmeyer’s model showed that batches P1 -P3 exhibited anomalous diffusion. The tablets formulated with PEG were as good as the commercial brand and they had an anomalous diffusion of the drug from the tablet; meaning that drug diffused following Fickian law and also diffused through a swollen and porous matrix. Kinetic plots and the DD solver can be used for fitting dissolution profiles to kinetic models. Keywords: Griseofulvin, Kinetics, Models, Surfactants, Polyethylene glycol (PEG) 4000, DD solver, Dissolution profile, mathematical models
... The diluent or ller used is lactose monohydrate because it has better mixing results on tablets with the wet granulation method. In addition, lactose is recommended as a ller than others because it is more stable when mixed and has excellent ow properties (Huang, 2013;Niazi, 2009). Polyvinylpyrrolidone or PVP K-30 is used as a binding agent because it has more than 10% solubility in water. ...
Figs knew playing vital roles in reducing cholesterol, strengthening the heart, and controlling respiration. Figs leaves extract with a dose of 50 mg/kg and 100 mg/kg can reduce triglyceride levels and can increase HDL cholesterol levels. This study aims to determine the effect of Ficus carica L. (fig) leaves extract on tablet dosage forms to reducing total cholesterol in rats induced with pork fat feed. Tablets were made by the wet granulation method in three formulas, there are F1 (extract dose 50 mg), F2 (extract dose 100 mg), and F3 (extract dose 150 mg), and compared with simvastatin tablets. The rats used in this study were 40 animals which were divided into 8 groups. Negative control group (induced of pork oil), F1 group, F2 group, F3 group, F4 group (placebo), positive control group (simvastatin 10 mg), base suspending agent group, and normal group.The average weight (mg) of F1 tablets (605.96 ± 9.94%), F2 (611.81 ± 12.33%), and F3 (639.09 ± 4.65%). As for the uniformity of size, all formulas have a diameter of 0.9 ± 0.0 (cm). for the hardness values of F1 (6.54 kg), F2 (5.31 kg), and F3 (5.43 kg). The value of friability F1 (0.8%), F2 (1.38%), and F3 (0.77%). While the disintegration time of F1 (13.31 minutes), F2 (19.48 minutes), and F3 (21.11 minutes). Whereas the dissolution rate (DE45) of each formulation decreased with increasing dose of extract, F1 (69.43%), F2 (64.95%), and F3 (60.04%). Extract contain quercetin as flavonoid, saponin, polyphenol, alkaloid, and tannin. Based on the results of statistical analysis, extract tablets did not differ significantly from simvastatin tablets in reducing total cholesterol levels. Tablet formulation of fig leaves extract with a dose variant has been shown to reduce total cholesterol in the blood between 18.3% until 37.98%.
... The sizes of the particles in DEM granules represent the typical size of the monohydrate lactose particles in pharmaceutical applications (Bonakdar & Ghadiri, 2018;Krok et al., 2016;Verheezen et al., 2004). Considering previous studies (Guenette et al. 2009;Huang et al. 2013;Mangwandi et al., 2010), it was shown in experimental particle size distribution data that typical size of monohydrate lactose particles is usually in the range 10-120 m. Therefore, the particles' size with 0.03; 0.037 and 0.05 mm in granule, belongs to d 10 -d 60 of this material's typical particle size. ...
Ball milling is widely used in industry to mill particulate material. The primary purpose of this process is to attain an appropriate product size with the least possible energy consumption. The process is also extensively utilised in pharmaceuticals for the comminution of the excipients or drugs. Surprisingly, for ball mill, little is known concerning the mechanism of size reduction. Traditional prediction approaches are not deemed useful to provide significant insights into the operation or facilitate radical step changes in performance. Therefore, the discrete element method (DEM) as a computational modelling approach has been used in this paper. In previous research, DEM has been applied to simulate breaking behaviour through the impact energy of all ball collisions as the driving force for fracturing. However, the nature of pharmaceutical material fragmentation during ball milling is more complex. Suitable functional equations which link broken media and applied energy do not consider the collision of particulate media of different shapes or collisions of particulate media (such as granules) with balls and rotating mill drum. This could have a significant impact on fragmentation. Therefore, this paper aimed to investigate the fragmentation of bounded particles into DEM granules of different shape/size during the ball milling process. A systematic study was undertaken to explore the effect of milling speed on breakage behaviour. Also, in this study, a combination of a density-based clustering method and discrete element method was employed to numerically investigate the number and size of the fragments generated during the ball milling process over time. It was discovered that the collisions of the ball increased proportionally with rotation speed until reaching the critical rotation speed. Consequently, results illustrate that with an increase of rotation speed, the mill power increased correspondingly. The caratacting motion of mill material together with balls was identified as the most effective regime regarding the fragmentation, and fewer breakage events occurred for centrifugal motion. Higher quantities of the fines in each batch were produced with increased milling speed with less quantities of grain fragments. Moreover, the relationship between the number of produced fragment and milling speed at the end of the process exhibited a linear tendency.
... mJ and the DSC curve of CLX powder revealed typical behavior of a crystalline anhydrous substance. The span 40 and cetyl alcohol, which form the nanovesicle after hydration, show sharp endothermic peaks at a similar temperature region at 50. [46,47]. Both plain and drug-loaded optimized formulations showed three peaks in the same regions. ...
Introduction:
Several recent studies have shown that the role of cyclooxygenase 2 (COX-2) in carcinogenesis has become more evident. It affects angiogenesis, apoptosis, and invasion, and plays a key role in the production of carcinogens. It has also been reported that COX-2 inhibitors such as celecoxib (CLX) might play an effective role in preventing cancer formation and progression. Formulation of CLX into nanovesicles is a promising technique to improve its bioavailability and anticancer efficacy.
Aim:
The aim of this study is to optimize and evaluate the anticancer efficacy of CLX-loaded in-situ provesicular powder composed of surfactants and fatty alcohol-based novel nanovesicles in-vitro and determine its pharmacokinetic parameters in-vivo.
Methods:
The novel provesicular powders were prepared by the slurry method and optimized by 32 full factorial design using the desirability function.
Results:
Small mean particle size was achieved by the formed vesicles with value of 351.7 ± 1.76 nm and high entrapment efficacy of CLX in the formed vesicles of 97.53 ± 0.84%. Solid state characterization of the optimized formulation showed that the powder was free flowing, showed no incompatibilities between drug and excipients and showed smooth texture. The cytotoxic study of the optimized formula on HCT-116, HepG-2, A-549, PC-3 and MCF-7 cell lines showed significant increase in activity of CLX compared to its free form. The pharmacokinetic study on albino rabbits after oral administration showed significant increase in the area under the curve (AUC)0-24 h and significantly higher oral relative bioavailability of the optimized formulation compared to Celebrex® 100 mg market product (p < 0.05).
Conclusion:
All findings of this study suggest the potential improvement of efficacy and bioavailability of CLX when formulated in the form of in-situ provesicular powder composed of surfactants and fatty alcohol-based novel nanovesicles for its repositioned use as an anticancer agent.
... In the last few decades, the formulation of low-dose tablet products has been increasingly developed [1]. From a formulation prospective, the British Pharmacopeia (BP) defined low-dose formulation as those formulations "containing less than 2 mg or 2% drug loading (w/w) of active pharmaceutical ingredients (API) [2,3]. ...
... According to the previous definitions, low-dose formulation has a relatively huge ratio of excipients to drug substance, which represent many obstacles during formulation and process development. Consequently, the manufacturing of low dose tablet formulations could be a challenging task due to (1) difficulty in obtaining proper content uniformity i.e. the level of uniformity in the quantity of the drug substance in each unit, which is the most quality attributes to produce effective and safe dosage unit; (2) low potency due to loss of drug during manufacturing process and (3) potential lack of stability due to the higher ratio of excipients to active substance and thus a probable loss of compatibility [4][5][6]. ...
Manufacture of low-dose tablet products has always the uniformity challenge. The objective of this work was to investigate the influence of key process variables of a gentle-wing high shear mixer on the uniformity of 1.0 % w/w albuterol sulphate/microcrystalline cellulose blend. Albuterol sulphate and excipients were mixed at various impeller and chopper speeds from 0.5 to 30 minutes. Triplicate samples were taken from nine different positions in the mixer bowl and the albuterol content was analyzed spectrophotometrically. Long mixing time (15 min) was necessary to achieve proper blend uniformity at low speeds of impeller and chopper. Otherwise, when the high chopper speed was applied, demixing occurred after 8 minutes with low impeller speed and after 6 minutes with high impeller speed. Furthermore, ANOVA analysis indicated the significant effect (P ≤ 0.05) of impeller speed and mixing time on the uniformity of the powder blends. Finally, dry mixing of low-dose based formulations in a gentle-wing high shear mixer; improving the dispersion of drug particles and formation of stable interactive mixture upon suitable selection of process variables. This study make the process variables of gentle-wing mixer a better candidate for further investigation and optimization using quality by design approach.
