RESUMEN
The deformulation stage of original drug products, which includes the quantification of critical excipients, is crucial for the successful development of generic drug products of solid dosage form. Sodium lauryl sulphate (SLS) belongs to the group of critical excipients due to its influence on the bioavailability of drugs, such as metformin. The purpose of this work is to carry out a feasibility study in order to develop a simple, economical, and robust analytical method for the quantification of SLS in metformin-containing tablets after their dissolution in water. Firstly, SLS is extracted with chloroform in acidic conditions, followed by the addition of methylene blue (MB) in order to form a SLS-MB ion pair, which is then measured photometrically at a wavelength of 651 nm. Additionally, interference from matrix components (excipients and APIs) was assessed, and it was found that metformin also forms a blue complex; therefore, this specific extraction method was developed. Other matrix components did not interfere with SLS determination. This method shows a well-estimated precision of 3.3% and accuracy of 5%, a calibration linearity of R2 = 0.99990, and a working range of 0.38 µg/mL to 10 µg/mL of SLS in water. The midpoint of the calibration graph corresponds to the concentration of SLS obtained by dissolving a single tablet in 1 L of water. This method seems appropriate for total SLS determination in tablets and can be applicable for deformulation.
RESUMEN
Compaction pressure can induce an undesirable solid-state polymorphic transition in drugs, fragmentation, loss of coated pellet integrity, and the decreased viability and vitality of microorganisms. Thus, the excipients with increased plasticity can be considered as an option to decrease the undesirable effects of compaction pressure. This study aims to increase the plasticity (to reduce the mean yield pressure; Py) of dried microcrystalline cellulose (MCC) by loading it with a specially selected plasticizer. Diethyl citrate (DEC), water, and glycerol were the considered plasticizers. Computation of solubility parameters was used to predict the miscibility of MCC with plasticizers (possible plasticization effect). Plasticizer-loaded MCC spheres with 5.0 wt.% of water, 5.2 wt.% of DEC, and 4.2 wt.% glycerol were obtained via the solvent method, followed by solvent evaporation. Plasticizer-loaded formulations were characterised by TGA, DSC, pXRD, FTIR, pressure-displacement profiles, and in-die Heckel plots. Py was derived from the in-die Heckel analysis and was used as a plasticity parameter. In comparison with non-plasticized MCC (Py = 136.5 MPa), the plasticity of plasticizer-loaded formulations increased (and Py decreased) from DEC (124.7 MPa) to water (106.6 MPa) and glycerol (99.9 MPa), and that was in full accordance with the predicted miscibility likeliness order based on solubility parameters. Therefore, water and glycerol were able to decrease the Py of non-plasticized MCC spheres by 16.3 and 30.0%, respectively. This feasibility study showed the possibility of modifying the plasticity of MCC by loading it with a specially selected plasticizer.
RESUMEN
Using microcrystalline cellulose (MCC) with plastic behaviour and calcium phosphate anhydrous (CaHPO4) with brittle behaviour under compaction is very popular in the pharmaceutical industry for achieving desirable structural-mechanical properties of tablet formulations. Thus, mixtures of specific grades of MCC and CaHPO4 were tested in volume proportions of 100-0, 75-25, 50-50, 25-75, and 0-100 at a constant weight-by-weight concentration of sodium stearyl fumarate lubricant, utilizing a state-of-the-art benchtop compaction simulator (STYL'One Nano). Tablet formulations were prepared at 100, 150, 250, 350, 450, and 500 MPa, and characterized by tabletability profile, ejection force profile, proportion-tensile strength relationship, proportion-porosity relationship, pressure-displacement, and elastic recovery profiles, as well as by in-/out-of-die Heckel plots and yield pressures. Interestingly, the 25-75 formulation demonstrated a two-stage out-of-die Heckel plot and was additionally investigated with X-ray micro-computed tomography (µCT). By post-processing the µCT data, the degree of brittle CaHPO4 particles falling apart, along with the increasing compression pressure, was quantified by means of the surface area to volume (S/V) ratio. For the 25-75 formulation, the first stage (up to 150 MPa) and second stage (above the 150 MPa) of the out-of-die Heckel plot could be attributed to predominant MCC and CaHPO4 deformation, respectively.
RESUMEN
Ethnobotanical reports from Latvia show that Tanacetum vulgare, Calluna vulgaris, Quercus robur, Artemisa absinthium, and Artemisia vulgaris contain phenolic compounds that have antioxidant properties, which can be beneficial in the treatment and prophylaxis of many diseases. The aim of this study was to characterize the phenolic compounds and antioxidant properties of these plants. Plant extracts were prepared using ethanol or acetone and then freeze-dried. Their total phenolic content (TPC), total flavonoid content (TFC), and total tannin content (TTC) were determined and characterized by HPLC. Their antioxidant properties were determined using a DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging assay. C. vulgaris herb and T. vulgare leaf extracts contained the highest amounts of flavonoids, but the bark of Q. robur had mostly tannins and phenolic acids. A. absinthium and A. vulgaris had the lowest amounts of polyphenols. When compared using extraction solvents, all acetone extracts had more TPC, more TFC, and better antioxidant activity. All plants contained chlorogenic acid, which contributes to antioxidant properties. The analysed plant extracts could be used in future studies to develop medicinal products with antioxidant properties.
RESUMEN
Flavonoids are hydroxylated polyphenols that are widely distributed in plants with diverse health benefits. Despite their popularity, the bioavailability of flavonoids is often overlooked, impacting their efficacy and the comparison of products. The study discusses the bioavailability-related physicochemical properties of flavonoids, with a focus on the poorly soluble compounds commonly found in dietary supplements and herbal products. This review sums up the values of pKa, log P, solubility, permeability, and melting temperature of flavonoids. Experimental and calculated data were compiled for various flavonoid subclasses, revealing variations in their physicochemical properties. The investigation highlights the challenges posed by poorly soluble flavonoids and underscores the need for enabling formulation approaches to enhance their bioavailability and therapeutic potential. Compared to aglycones, flavonoid glycosides (with sugar moieties) tend to be more hydrophilic. Most of the reviewed aglycones and glycosides exhibit relatively low log P and high melting points, making them "brick dust" candidates. To improve solubility and absorption, strategies like size reduction, the potential use of solid dispersions and carriers, as well as lipid-based formulations have been discussed.
RESUMEN
Purpose: The study examined the pharmacokinetic profile of fixed formulation mixtures comprising 225 mg of ropivacaine for local infiltration analgesia with or without epinephrine, and femoral nerve block in older patients presenting for orthopedic surgery and explored potential influences of block type, age, and body weight on this profile. Patients and Methods: Twenty four patients scheduled for total knee arthroplasty were randomly assigned to three groups: femoral nerve block, local infiltration analgesia with epinephrine and local infiltration analgesia without epinephrine. Blood samples were collected at 10, 30, 60, and 120 min following the block and total plasma concentrations of ropivacaine were quantified by high performance liquid chromatography. Results: The mean individual peak total plasma concentrations of ropivacaine in local infiltration analgesia with and without epinephrine, and femoral nerve block group were 0.334, 0.490 and 0.545 µg mL-1 (p = 0.16). Local infiltration with epinephrine group had significantly lower plasma ropivacaine concentrations at 30, 60 and 120 minutes. The plasma ropivacaine concentrations exceeded 2.2 µg mL-1 in one patient. Age, but not body weight, had a moderate correlation with peak plasma ropivacaine concentration (r = 0.37, p = 0.08). Conclusion: Administration of a fixed 225 mg dose of ropivacaine for local infiltration analgesia with epinephrine and femoral nerve block results in plasma ropivacaine concentrations below the toxicity threshold, indicating their safety. The use of local infiltration analgesia with epinephrine provides a greater safety margin, as local infiltration analgesia without epinephrine may lead to ropivacaine concentrations associated with symptoms of local anesthetic toxicity.
RESUMEN
The growing market of herbal medicines, the increase in international trade in Latvia, and the lack of adequate analytical methods have raised the question of the potential use of herbal fingerprinting methods. In this study, high-performance liquid chromatography (HPLC) and thin layer chromatography (TLC) methods were developed for obtaining chromatographic fingerprints of four taxonomically and evolutionary different medicinal plants (Hibiscus sabdariffa L., Calendula officinalis L., Matricaria recutita L., Achillea millefolium L.). Retention time shifting, principal component analysis (PCA), hierarchical cluster analysis (HCA), and orthogonal projections to latent structures (OPLS) analysis were used to improve and analyze the obtained fingerprints. HPLC data detection at 270 nm was determined superior to 360 nm for the distinction of medicinal plants and used data alignment method significantly increased similarity between samples. Analyzed medicinal plant extracts formed separate, compact clusters in PCA, and the results of HCA correlated with the evolutionary relationships of the analyzed medicinal plants. Herbal fingerprinting using chromatographic analysis coupled with multivariate analysis has a great potential for the identification of medicinal plants as well as for the distinction of Latvian native medicinal plants.