Comparative evaluation of humic substances in oral drug delivery (original) (raw)
Related papers
Role of humic acid on oral drug delivery of an antiepileptic drug
Drug Development and Industrial Pharmacy, 2011
Context: Humic acid (HA) is omnipresent in natural organic matter that is a macromolecular, negatively charged polyelectrolyte that contains a hydrophobic core. It is also present in a significant amount in Shilajit (used frequently in traditional medicines), which is used in this study as a source of extraction. HA is evaluated for the oral drug delivery of carbamazepine (CBZ). Objective: HA is used in this study to increase the dissolution, intestinal permeation, and pharmacodynamic response of CBZ (bio pharmaceutics classification system (BCS) II) by the technique of complexation and other related mechanism reported with humic substances. Methods: Different complexation techniques were explored in this study for the entrapment of CBZ, which was authenticated by molecular modeling and conformational analysis. These were further characterized using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), and X-ray diffraction (XRD). Solubility analysis and dissolution release profile were carried out to access the in vitro parameters. For ex vivo studies, rat gut intestinal permeability was done. And finally pharmacodynamic evaluation (maximal electroshock method) was carried out for optimized complexes. Results: Molecular modeling approach and instrumental analysis (DSC, XRD, and FT-IR) confirmed the entrapment of CBZ inside the complexing agent. Increased solubility (∼1742%), sustained release (∼78%), better permeability (∼3.5 times), and enhanced pharmacodynamic responses conferred the best to 1:2 freeze dried (FD) and then 1:2 kneading (KD) complexes compared with pure CBZ. Conclusion: Now it could be concluded that HA may be tried as a complexing agent for antiepileptic drug and other classes of low water-soluble drug.
Effect of Fulvic Acid on Oral Delivery of Carbamazepine
Science of Advanced Materials, 2011
Shilajit has been used in traditional system of medicine since antiquity which is also a rich source of humic substances (Humin, Humic acid and Fulvic acid). These least explored macromolecular humic substances possess several unique properties. Here the Complexation property of Fulvic acid with Carbamazepine is explored for the first time and different in vitro, ex vivo and pharmacodynamic parameters are evaluated. Complexes were evaluated by Differential scanning calorimetry, Fourier transform infra red spectroscopy, X-ray diffraction, solubility analysis, release profile study, computational method and molecular modeling. Optimized complexes were undergone, permeation study across intestine, anticonvulsant activity (Maximal Electro Shock) and biochemical estimations (TBARS and glutathion). These studies confirmed the entrapment efficiency of the fulvic acid. Increased solubility (2268.75%), better release profile (∼81% in 60 min), rat intestinal permeability (>3 times), biochemical and pharmacodynamic studies conferred the best to freeze dried (ratio; 1:2) and kneading (ratio; 1:2) complexes.
International Journal of Applied Pharmaceutics, 2019
Efficiency of therapeutic compounds could be enhanced by encapsulation and covalent attachments to a biomaterial carrier. Complex formation with humic substances is valuable techniques to improve bioactivity of natural products. Fractal structures of humic substances also have adjacent carboxyl and hydroxyl groups. Along with molecular bonding property, reduction-oxidation and association-dissociation capacities of humic substances are considered this as a biomaterial for transform, other molecules, and substances. Immune system responses of humic acid stimulates in the human body. However, pharmaceutical importance of humic substances, demands on evidenced efficacy and a clearly defined chemical composition of the preparations used. Toxicological safety standards also have to be evaluated. This review summarises the application of humic substances as pharmaceuticaly important biomaterial. Research on this zone opened up an application for humic substances in pharmacogonasy.
Humic Substances as a Potent Biomaterials for Therapeutic and Drug Delivery System-A Review
International Journal of Applied Pharmaceutics, 2019
Efficiency of therapeutic compounds could be enhanced by encapsulation and covalent attachments to a biomaterial carrier. Complex formation with humic substances is valuable techniques to improve bioactivity of natural products. Fractal structures of humic substances also have adjacent carboxyl and hydroxyl groups. Along with molecular bonding property, reduction-oxidation and association-dissociation capacities of humic substances are considered this as a biomaterial for transform, other molecules, and substances. Immune system responses of humic acid stimulates in the human body. However, pharmaceutical importance of humic substances, demands on evidenced efficacy and a clearly defined chemical composition of the preparations used. Toxicological safety standards also have to be evaluated. This review summarises the application of humic substances as pharmaceuticaly important biomaterial. Research on this zone opened up an application for humic substances in pharmacogonasy.
Future of Humic substances as Pharmaceutical Excipient
Humic Substances (HS) occur naturally in our environment and are the remains of a process called humification, which is the biodegradation of biomass that then recombines and converts into dark colored complex compounds with no definite chemical structure. These are the end result of microbial degradation but resistant to further microbial degradation. It has a strong global presence as a dietary supplement and cosmetics applications for different beneficial uses. Till date its exploration as a pharmaceutical excipient has been limited to academic research only but the data being presented augurs a good commercial success.
Indian Journal of Pharmaceutical Education and Research, 2020
Objectives: The present study is aimed to develop and evaluate Carbamazepine tablets using ternary solid dispersed product. Carbamazepine belongs to BCS class II having low solubility. Ternary system was formulated with biosurfactant and water-soluble polymers to enhance dissolution rate and bioavailability. Methods: Binary and ternary solid dispersion was prepared using hydroxyl propyl methyl cellulose (HPMC) K-100, Polyvinyl pyrolidine (PVP) K-30 and Poly ethylene glycol (PEG) 6000 as a polymer and biosurfactant respectively by solvent evaporation method and evaluated for drug content uniformity and in-vitro dissolution study. Carbamazepine tablet were prepared by incorporation of ternary solid dispersed product along with other excipients by direct compression technique. Prepared formulations were evaluated for pre-compression and post-compression parameters. Oral toxicity study of biosurfactant was performed using female wistar rats. Results: In-vitro dissolution profile of optimized tablet formulation OF1 and OF2 showed 75.14% and 71.26% release in 1.2 pH respectively and similarly at 6.8 pH buffer 64.33% and 58.96% respectively. Pre-compression and postcompression values of formulated tablets were within the specified acceptable limits. In-vivo dissolution study of optimized formulation OF1 showed an increase in dissolution rate in accordance with pure drug. Oral toxicity study of biosurfactant was safe at 2000 mg per kg body weight of rat. Short term stability of the optimized formulation was stable without deviations at room temperature. Conclusion: Addition of biosurfactant in ternary solid dispersion system proved to be promising excipient in formulation of carbamazepine tablet for enhanced dissolution rate, dose reduction and bioavailability.
Journal of Separation Science, 2016
A new humic acid based stationary phase has been used, for the first time, to achieve the separation and quantification of paracetamol and caffeine in pharmaceutical preparations under reversed-phase high-performance liquid chromatography conditions. Central composite design was applied as a powerful tool to optimize the most dominant parameters that influence the resolution of reversed-phase high-performance liquid chromatography, that is, mobile phase composition (acetonitrile percentage in water), flow rate, and column temperature. The optimum conditions were obtained as 21.69%, 1.5 mL/min, and 15ЊC, respectively, with the aid of a second-order quadratic model and desirability function. Under the optimum conditions, the peaks could be baseline separated within 10 min. For the developed reversed-phase high-performance liquid chromatography method, the linearity was investigated in the concentration ranges of 2-160 mg/mL (R 2 = 0.999) for paracetamol and 2-9.9 mg/mL (R 2 = 0.991) for caffeine. Mean recoveries for paracetamol and caffeine were 95.90 and 95.68%, respectively. The limits of detection and quantification were 4.1 × 10-4 and 1.3 × 10-3 mg/mL for paracetamol and 1.6 × 10-4 and 5.0 × 10-4 mg/mL for caffeine. The results showed that the new humic acid based stationary phase is very suitable for the separation of paracetamol and caffeine in pharmaceutical preparations and, thus it can be used effectively in the pharmaceutical industry.
International Journal of Applied Pharmaceutics, 2024
Objective: Study of physical and chemical activity of biologically active substances containing humic complexes (HCs). Comparison of various preparations available on the market. Development of a modern express method of quality control. Methods: Preparations containing HCs manufactured by Biotechnology System, BIODORON, Faberlic, etc. Built-in flux density sensor TES-92 (TES Electrical Electronic Corp., Taipei, Taiwan), which was used to determine the flux density of radio thermal emission in the g igahertz range. Zetasizer Nano ZSP (Malvern Panalytical, Worcestershire, UK) was used to determine the size of nanoparticles in preparations containing the HCs and MP with humic acids (HAs). Results: In the course of experiments for studying the intrinsic radiothermal emission of HAs preparations, differences were found between HAs from different manufacturers; for example, HAs produced by a biotechnology system with a flux density of 35±5 µW/m 2 at 37 °C differs several times from similar preparations produced by other companies. When diluting HAs from Biotechnology System 10, 100 and 1000 times, the emissivity of the preparations is preserved. Also, with the expiration of the 2 y shelf life of the preparation, as stated by the manufacturer, a sharp drop in emissivity of 20 times is observed. Conclusion: The radiothermal activity of HAs preparations revealed during the experiments allows the developing a method that can be utilized to control the quality of manufactured products, as well as control the expiration dates of preparations without opening the primary package.
International Journal of Drug Delivery, 2010
Oral extended release products offer potential advantages in patient compliance and therapeutic outcomes like sustained blood levels with attenuation of adverse effects. In neuropsychiatric disorders like depression, most of the formulations serve a marketing objective rather than a clinical objective. The present investigation was aimed to develop a once daily sustained release formulation for delivery of an acid-labile, water soluble antidepressant, duloxetine HCl. The formulation was pragmatically designed using blend of natural and synthetic polymeric biomaterials that it releases the drug at alkaline pH in a sustained manner. The basic intention was to develop a tablet formulation with hydrophilic matrix core, using blend of release retarding natural biodegradable polymers such as guar gum, carbopol 71G-NF (a synthetic carbomer) and C-Pharm ® gel. Barrier coating using HPMC-E5 was given to retard the initial release followed by enteric coating with HPMC-AS to prevent exposure of drug in acidic mileau of the stomach. The formulation exhibited desired release pattern and was described best-fit by Hixon-Crowell model. Stability analysis under stress conditions up to one month displayed good reproducibility. The matrix tablets successfully decreased the symptoms of depression (significant decrease in immobility time) in a rat forced swimming model. Pharmacokinetic data of the formulation revealed (t max ~ 6 h, C max ~ 1157.58 ng/ml, mean AUC t~1 1145.04 ng*h/ml, and K a~1 .07h-1) good correlation in all animals.
Bioavailability Study of Physical Mixture of Carbamazepine and Amino Acids Dewi Isadiartuti
2015
Objective: This study aimed to evaluate the bioavailability of physical mixture (PM) of carbamazepine (CBZ) and amino acids (glycine, alanine, and lysine), includes a parameter t max , C max and AUC 0-12 . Methods: PM made by weighing CBZ with amino acids (glycine, alanine, and lysine) equimolar and mix both components with a mortar until a homogeneous mixture. PM obtained was characterized using differential thermal analysis (DTA), Fourier transform infrared (FTIR) and optical microscopy. Bioavailability was conducted after obtaining ethical clearance from Faculty of Veterinary Airlangga University to five New Zealand Rabbits for each treatment. CBZ levels in blood plasma were determined by HPLC analysis method. Results: The results of the DTA thermogram and infrared spectra showed that CBZ compound mixed with the components of the constituent amino acids. Time achieve maximum levels value (t max ) PM of CBZ-GLY, CBZ-ALA, and CBZ-LYS, respectively, for 5.09, 3.85, and 3.93 hours fa...