Evaluation of Dissolution Profiles of a Newly Developed Solid Oral Immediate-Release Formula Containing Alpha-Lipoic Acid

Abstract

Alpha-lipoic acid (ALA, thioctic acid), a naturally-occurring essential dithiol compound, has become a common ingredient in many pharmaceutical and food supplement products (FSP), used in oxidative stress-dependent pathologies; oral bioavailability of ALA is limited by pharmacokinetic particularities that reduce its therapeutic efficacy-reduced solubility, lack of gastric stability and hepatic degradation, doubled by formulation hinders. The objectives were to develop a solid oral 600 mg ALA FSP to obtain an optimal pharmaceutical profile compared to a reference listed drug (RLD) with a similarity factor f2 50. A comparative dissolution study was performed; an HPLC method was used for ALA quantification. After planning combinatory simulations (formulation stage), two prototype formulas (#1 and #2) were manufactured and further optimized by adjusting ALA physical characteristics and the excipients quantities (#3 and #4) in order to achieve the Quality Target Product Profile. A misshapen of ALA’s in vitro release was observed for #3 Formula (f2 = 31.6); the optimal profile was obtained for Formula #4 (f2 = 58.5). A simple quantitative formula is not enough to assure good ALA bioavailability; the formulation needs multiple compounding modulations under physicochemical compatibility algorithms, with multiple dissolution profiles testing back-ups. It is essential to ensure a formulation with an in vitro dissolution comparable with the RLD, allowing the compound to reach its target level to assure the optimum claimed antioxidant activity of ALA at the cellular level, even for food supplement formulations.

Manufacturing and Assessing the New Orally Disintegrating Tablets, Containing Nimodipine-hydroxypropyl-β-cyclodextrin and Nimodipine-methyl-β-cyclodextrin Inclusion Complexes

“…The uniformity of the tablet sizes offers information on the compression process, as it is well known that thickness may vary, with no weight change, due to the material difference in density or the applied force [ 46 ]. The mass uniformity represents an indicator for a well-conducted compression process and for an accurate dosage of the tablets [ 47 ].…”

Design and Evaluation of Orally Dispersible Tablets Containing Amlodipine Inclusion Complexes in Hydroxypropyl-β-cyclodextrin and Methyl-β-cyclodextrin

“…The type of cyclodextrin did not much affect the tablets’ mechanical resistance, as the F7 had 44 N and F9 had 42.2 N hardness. Still, even if the tablets exhibit great hardness, they can show unsatisfactory capping or lamination propensity [ 58 ]. Consequently, friability must be analyzed in order to establish a tablet’s ability to withstand handling before usage.…”

Study Regarding a New Extended-Release Calcium Ascorbate and Hesperidin Solid Oral Formulation

“…The release of ascorbic acid in prolonged-release tablets was assessed by an in vitro dissolution test: 900 mL distilled water as dissolution medium, baskets dissolution apparatus, 50 rpm, 480 minutes dissolution time, 37 ± 0.5°C temperature. In addition, the amount of dissolved calcium ascorbate was assessed by adapting volumetric titration used for vitamin C assay; sampling times were one and 8 hours [27]. Acceptability criteria: The dissolved calcium ascorbate content must be 20 ÷ 40% dissolved after one hour and at least 70% after 8 hours.…”

“…For long-term ascorbic acid use, high demand for good pharmacokinetic profiles and improved gastric tolerance was welcomed [32,33]. However, in vivo, bioavailability studies and digestibility studies may be developed to perform more accurate pharmacokinetic profiles [27]. The present research has limitations, as it used only in vitro studies to assess the release profile of the active compound, ascorbic acid.…”