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.
Highlights
The lipoic acid (α-lipoic acid, alpha-lipoic acid, thioctic acid, ALA, LA, Synonym: (±)1,2-Dithiolane-3-pentanoic acid, 6,8-Dithiooctanoic acid, DL-α-Lipoic acid, DL-6,8-Thioctic acid, Lip (S2), Thioctic acid) (CAS number: 1200-22-2) [1] is an eight-carbon organosulfur fatty acid derived from caprylic acid
The recent literature shows continuous research on improving the Biopharmaceutics Classification System (BCS) class II ALA biodisponibility through formulation adjustments to achieve a higher bioavailability (Cmax and AUC values) and decreased time to maximum concentration (Tmax) and T1/2. This goal is achieved by several approaches, using the natural stereoisomer R-lipoic acid (RLA) and the sodium salt (NaRLA), complexation with octenylsuccinylated high-amylose starch [90]; by encapsulation and stabilization in cyclodextrin inclusion complex [91], incorporation in natural polysaccharide-based gel beads [92], cyclodextrin inclusion complex electrospun nanofibers [93] and others; these forms are under development and not available in the current therapy
In order to develop a product based on alpha-lipoic acid, a micronutrient with several pharmacological as well as antioxidant properties, in a concentration of 600 mg per tablet, with oral administration and immediate release, we have performed the pharmaceutical development taking into account technological and dissolution aspects-compared to the reference listed drug (RLD)
Summary
The lipoic acid (α-lipoic acid, alpha-lipoic acid, thioctic acid, ALA, LA, Synonym: (±)1,2-Dithiolane-3-pentanoic acid, 6,8-Dithiooctanoic acid, DL-α-Lipoic acid, DL-6,8-Thioctic acid, Lip (S2), Thioctic acid) (CAS number: 1200-22-2) [1] is an eight-carbon organosulfur fatty acid derived from caprylic acid (octanoic acid). ALA is synthesized in trace quantities in animals, found in microorganisms, plants, and animals [2,3]; humans obtain ALA via de novo mitochondrial synthesis or from food [4,5] animal-derived ALA via de novo mitochondrial synthesis or from food [4,5] animal-derived (red meat, liver, haneadrtk,iadnndeyk)idonrepy)laonrtps l(asnptisn(ascphin, abcrho,cbcorolic,ctoolmi, taotmoeast,oBersu, Bssreuls’sseslp’srsopurtosu, tpso, tpaottoaetso,egs,arden gardepnepaesa, sa,nadndricriecebrbarna)n)[6[,67,]7.].AALLAA ffuunnccttiioonnss iinn tthhee bbooddyy,, mmuucchhlilkikeeaaBB-v-vitiatmaminin. AisLaA is a cofactcoorffaocrtosrevfoerrasleevnerzaylmenesz,yimncelsu,dinincglupdyinrugvpayterudveahtyeddreohgyednraosgeecnoamsepcleoxm(pPlDexH(;PEDCH) a; nEdC) and α-ketoαg-lkuettaorgaltuetadreahteydreohgyednraosgeencaosmepcolemxp(KleDx H(K;DEHC;),EtCw),otwenozeynmzeysmleoscalotecadteind imnimtoicthoochno-ndria dria aannddininvvoolvlveeddinineenneerrggyypprroodduucctitoionn[[1177]]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
