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Curcumin Formulations for Better Bioavailability
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<blockquote data-quote="madman" data-source="post: 269284" data-attributes="member: 13851"><p><strong>ABSTRACT</strong></p><p></p><p><em><strong>Curcumin has been credited with a wide spectrum of pharmacological properties for the prevention and treatment of several chronic diseases such as arthritis, autoimmune diseases, cancer, cardiovascular diseases, diabetes, hemoglobinopathies, hypertension, infectious diseases, inflammation, metabolic syndrome, neurological diseases, obesity, and skin diseases. </strong>However, due to its weak solubility and bioavailability, it has limited potential as an oral medication. Numerous factors including low water solubility, poor intestinal permeability, instability at alkaline pH, and fast metabolism contribute to curcumin’s limited oral bioavailability. In order to improve its oral bioavailability, different formulation techniques such as coadministration with piperine, incorporation into micelles, micro/nanoemulsions, nanoparticles, liposomes, solid dispersions, spray drying, andnoncovalent complex formation with galactomannosides have been investigated with in vitro cell culture models, in vivo animal models, and humans. <strong>In the current study, we extensively reviewed clinical trials on various generations of curcumin formulations and their safety and efficacy in the treatment of many diseases. We also summarized the dose, duration, and mechanism of action of these formulations. We have also critically reviewed the advantages and limitations of each of these formulations compared to various placebo and/or available standard care therapies for these ailments.</strong> <strong>The highlighted integrative concept embodied in the development of next-generation formulations helps to minimize bioavailability and safety issues with least or no adverse side effects and the provisional new dimensions presented in this direction may add value in the prevention and cure of complex chronic diseases.</strong></em></p><p></p><p></p><p></p><p></p><p><strong>2. BIOAVAILABILITY OF CONVENTIONAL CURCUMIN</strong></p><p></p><p><em>These studies indicated that the method of administration (whether oral or intravenous) affects the serum levels of curcumin and further suggest that the serum achievable concentrations of curcumin in humans and rats are not exactly comparable. Hence, it is not only imperative to develop bioavailable curcumin but also equally important to find the safety and efficacy of these formulations in humans.</em></p><p></p><p></p><p></p><p></p><p><strong>4. CURCUMIN FORMULATIONS</strong></p><p><strong></strong></p><p><strong><em>4.1. First-generation curcumin formulation</em></strong></p><p></p><p><em>Taken together, these results indicated that the first-generation curcumin formulations enhanced the absorption and bioavailability of pure curcumin and were effective against various ailments including autoimmune diseases, cancer, diabetes, hemoglobinopathies, oral diseases, and PMS.</em></p><p><em></em></p><p><em></em></p><p><em><strong>4.2. Second-Generation Curcumin Formulation</strong></em></p><p><em></em></p><p><em>Collectively, these studies suggest that second-generation formulations of curcumin improved the bioavailability of curcumin and their significance drives the ancillary goal to develop them as therapeutic drugs.</em></p><p></p><p></p><p><strong><em>4.3. Third-Generation Curcumin Formulation</em></strong></p><p></p><p><em>Certainly, these clues warrant further investigations on third-generation curcumin formulations as a novel nutraceutical formulation in diagnosing and treating various ailments.</em></p><p></p><p></p><p></p><p></p><p><strong>5. CONCLUSION</strong></p><p><strong></strong></p><p><strong><em>Advances in chemistry and technologies have provided the versatility and tools to develop a range of innovative curcumin formulations with considerable improvement in oral bioavailability and safety. <u>Decades of research on curcumin and its formulations resulted in the increased oral bioavailability of curcumin from 11 ng/mL to 626.98 μg/mL</u>. <u>These curcumin formulations were found to be safe and well-tolerated even at higher doses ranging from 2 g/day to 12 g/day and for a prolonged duration of 6 months to a year</u>. <u>The simplest first-generation formulation with adjuvants to second-generation with polysorbates to third-generation with only natural material have shown tremendous absorption capacity, cellular uptake, and safety not only in diseased but also in healthy subjects providing evidence of disease prevention and treatment capability of these formulations</u>. <u>As we noted at this time, a few of these regimens including curcumin plus piperine combination, BCM-95, nano curcumin, Meriva, and Theracurmin have been tested clinically and are effective against chronic diseases such as arthritis, autoimmune diseases, cancer, and diabetes, endometriosis, hemoglobinopathies, metabolic syndrome, neurological disorders, obesity, oral diseases, psychological disorders, and skin diseases</u>. All the formulations have been shown beneficial effects compared to either placebo such as calcium phosphate, lactose, rice flour, and starch, or the standard care treatment. Major grade 3 side effects, GI intolerance, and hepatotoxicity were reported when curcumin was administered intravenously earlier. <u>Nevertheless, the minor side effects in most of these trials with oral intake of curcumin formulations include cold, irritation, indigestibility, and nausea which in a few cases might be attributed to adjuvants and emulsifiers</u>. However, clinical studies are scarce at this time on upcoming and more promising third-generation formulations. <u>Notably, it is advisable to opt for highly bioavailable curcumin formulations that have demonstrated their therapeutic efficacy at a relatively low dosage of 80−500 mg/day</u>. <u>Further, most of the clinical trials conducted were restricted to a small number of patient groups</u>. However, more research is needed to examine the safety and effectiveness of curcumin formulations in both large and diverse patient populations with different phases of the disease. <u>As such, all these formulations cannot be inherently compared due to dissimilarities in the dose, duration of treatment, clinical study design, formulation type, the method used for analysis, and population disparity</u>. Recently, as detailed earlier, curcumin formulation was also used to diagnose the amyloid spots clinically. Therefore, curcumin formulations have significant potential to serve as preventive, diagnostic, and therapeutic entities.</em></strong></p></blockquote><p></p>
[QUOTE="madman, post: 269284, member: 13851"] [B]ABSTRACT[/B] [I][B]Curcumin has been credited with a wide spectrum of pharmacological properties for the prevention and treatment of several chronic diseases such as arthritis, autoimmune diseases, cancer, cardiovascular diseases, diabetes, hemoglobinopathies, hypertension, infectious diseases, inflammation, metabolic syndrome, neurological diseases, obesity, and skin diseases. [/B]However, due to its weak solubility and bioavailability, it has limited potential as an oral medication. Numerous factors including low water solubility, poor intestinal permeability, instability at alkaline pH, and fast metabolism contribute to curcumin’s limited oral bioavailability. In order to improve its oral bioavailability, different formulation techniques such as coadministration with piperine, incorporation into micelles, micro/nanoemulsions, nanoparticles, liposomes, solid dispersions, spray drying, andnoncovalent complex formation with galactomannosides have been investigated with in vitro cell culture models, in vivo animal models, and humans. [B]In the current study, we extensively reviewed clinical trials on various generations of curcumin formulations and their safety and efficacy in the treatment of many diseases. We also summarized the dose, duration, and mechanism of action of these formulations. We have also critically reviewed the advantages and limitations of each of these formulations compared to various placebo and/or available standard care therapies for these ailments.[/B] [B]The highlighted integrative concept embodied in the development of next-generation formulations helps to minimize bioavailability and safety issues with least or no adverse side effects and the provisional new dimensions presented in this direction may add value in the prevention and cure of complex chronic diseases.[/B][/I] [B]2. BIOAVAILABILITY OF CONVENTIONAL CURCUMIN[/B] [I]These studies indicated that the method of administration (whether oral or intravenous) affects the serum levels of curcumin and further suggest that the serum achievable concentrations of curcumin in humans and rats are not exactly comparable. Hence, it is not only imperative to develop bioavailable curcumin but also equally important to find the safety and efficacy of these formulations in humans.[/I] [B]4. CURCUMIN FORMULATIONS [I]4.1. First-generation curcumin formulation[/I][/B] [I]Taken together, these results indicated that the first-generation curcumin formulations enhanced the absorption and bioavailability of pure curcumin and were effective against various ailments including autoimmune diseases, cancer, diabetes, hemoglobinopathies, oral diseases, and PMS. [B]4.2. Second-Generation Curcumin Formulation[/B] Collectively, these studies suggest that second-generation formulations of curcumin improved the bioavailability of curcumin and their significance drives the ancillary goal to develop them as therapeutic drugs.[/I] [B][I]4.3. Third-Generation Curcumin Formulation[/I][/B] [I]Certainly, these clues warrant further investigations on third-generation curcumin formulations as a novel nutraceutical formulation in diagnosing and treating various ailments.[/I] [B]5. CONCLUSION [I]Advances in chemistry and technologies have provided the versatility and tools to develop a range of innovative curcumin formulations with considerable improvement in oral bioavailability and safety. [U]Decades of research on curcumin and its formulations resulted in the increased oral bioavailability of curcumin from 11 ng/mL to 626.98 μg/mL[/U]. [U]These curcumin formulations were found to be safe and well-tolerated even at higher doses ranging from 2 g/day to 12 g/day and for a prolonged duration of 6 months to a year[/U]. [U]The simplest first-generation formulation with adjuvants to second-generation with polysorbates to third-generation with only natural material have shown tremendous absorption capacity, cellular uptake, and safety not only in diseased but also in healthy subjects providing evidence of disease prevention and treatment capability of these formulations[/U]. [U]As we noted at this time, a few of these regimens including curcumin plus piperine combination, BCM-95, nano curcumin, Meriva, and Theracurmin have been tested clinically and are effective against chronic diseases such as arthritis, autoimmune diseases, cancer, and diabetes, endometriosis, hemoglobinopathies, metabolic syndrome, neurological disorders, obesity, oral diseases, psychological disorders, and skin diseases[/U]. All the formulations have been shown beneficial effects compared to either placebo such as calcium phosphate, lactose, rice flour, and starch, or the standard care treatment. Major grade 3 side effects, GI intolerance, and hepatotoxicity were reported when curcumin was administered intravenously earlier. [U]Nevertheless, the minor side effects in most of these trials with oral intake of curcumin formulations include cold, irritation, indigestibility, and nausea which in a few cases might be attributed to adjuvants and emulsifiers[/U]. However, clinical studies are scarce at this time on upcoming and more promising third-generation formulations. [U]Notably, it is advisable to opt for highly bioavailable curcumin formulations that have demonstrated their therapeutic efficacy at a relatively low dosage of 80−500 mg/day[/U]. [U]Further, most of the clinical trials conducted were restricted to a small number of patient groups[/U]. However, more research is needed to examine the safety and effectiveness of curcumin formulations in both large and diverse patient populations with different phases of the disease. [U]As such, all these formulations cannot be inherently compared due to dissimilarities in the dose, duration of treatment, clinical study design, formulation type, the method used for analysis, and population disparity[/U]. Recently, as detailed earlier, curcumin formulation was also used to diagnose the amyloid spots clinically. Therefore, curcumin formulations have significant potential to serve as preventive, diagnostic, and therapeutic entities.[/I][/B] [/QUOTE]
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