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Licensed Unlicensed Requires Authentication Published online by De Gruyter April 5, 2021

Pharmacokinetics of solid lipid Boswellia serrata particles in healthy subjects

Preeti D. Kulkarni EMAIL logo , Neena D. Damle , Lal Hingorani , Vaidhun H. Bhaskar , Minal R. Ghante , Anand Patil , Murari Gurjar and Vikram Gota

Abstract

Objectives

The anti-inflammatory activity of Boswellia serrata extracts (BSE) is well known. BSE comprises boswellic acids (BA) such as 3-O-acetyl-11-keto-beta-boswellic acid (AKBA) and 11-keto-boswellic acid (KBA) as major constituents. One of the limitations of BAs is their poor oral bioavailability. The aim of the study was to prepare solid lipid particles of Boswellia serrata extract (SLBSP) to enhance the bioavailability of BAs.

Methods

The pharmacokinetic profile of BAs was studied in 10 healthy human volunteers following a single oral dose of 333 mg of SLBSP. Pharmacokinetic blood samples were collected at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 h post drug administration. Plasma KBA and AKBA levels were measured using a validated LC-MS/MS method. Pharmacokinetics parameters were estimated using Pheonix WinNonlin (Build 6.4.0.768) software.

Results

Ten healthy human volunteers were included and peak plasma concentration was achieved in 1.5 and 2.3 h for AKBA and KBA respectively. Maximum plasma concentration (Cmax) was 8.04 ± 1.67 ng/mL for AKBA and 23.83 ± 4.41 ng/mL for KBA whereas the corresponding area under the concentration-time curve (AUC) was 136.7 ± 56.77 ng/mL*h and 165.7 ± 24.5 ng/mL*h respectively. The elimination half-life (t1/2) of AKBA and KBA was 6.8 ± 3.0 h and 2.45 ± 0.3 h respectively.

Conclusions

The SLBSP formulation of BSE showed enhanced oral bioavailability of BAs compared with historically reported data of unformulated BSE.


Corresponding author: Dr. Preeti D. Kulkarni, Associate Professor and HOD, Department of Quality Assurance, Gahlot Institute of Pharmacy, Koparkhairane, Navi Mumbai, 400709, India; and School of Pharmacy and Medical Science, Singhania University, Pacheri Bari, Jhunjhunu, 333515, Rajasthan, India, Phone: +91 22 27550816, E-mail:

Funding source: Pharmanza Herbal Pvt. Ltd.

Award Identifier / Grant number: P-RIGS18-028-0028

Acknowledgments

The authors thank Mr.Amol P. Deshmukh who assisted us in the construction of manuscript through his medical writing support. Also, the authors acknowledge Pharmanza Herbal Pvt. Ltd. for providing Wokvida for study.

  1. Research funding: The study was funded by Pharmanza Herbal Pvt. Ltd., Dharmaj, Gujarat, India.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: The study was approved by the Institutional Ethics Committee of DY Patil Institute for Ayurvedic Medicine, Navi Mumbai, and conducted in compliance with the World Medical Association Declaration of Helsinki regarding ethical conduct of research involving human subjects.

References

1. Neogi, T. The epidemiology and impact of pain in osteoarthritis. Osteoarthritis Cartilage 2013;21:1145–53. https://doi.org/10.1016/j.joca.2013.03.018.Search in Google Scholar

2. Al-Saeed, A. Gastro intestinal and cardiovascular risk of nonsteroidal anti-inflammatory drugs. Oman Med J 2011;26:385–91.10.5001/omj.2011.101Search in Google Scholar

3. Aggarwal, B, Prasad, S, Reuter, S, Kannappan, R, Yadav, V, Park, B, et al.. Identification of novel anti-inflammatory agents from ayurvedic medicine for prevention of chronic diseases: “reverse pharmacology” and “bedside to bench” approach. Curr Drug Targets 2011;12:1595–653.10.2174/138945011798109464Search in Google Scholar

4. Alam, M, Khan, H, Samiullah, L, Siddique, K. A review on phytochemical and pharmacological studies of Kundur (Boswellia serrata roxb ex colebr.)-A unani drug. J Appl Pharmaceut Sci 2012;02:148–56.Search in Google Scholar

5. Gupta, P, Samarakoon, S, Chandola, H, Ravishankar, B. Clinical evaluation of Boswellia serrata (Shallaki) resin in the management of Sandhivata (osteoarthritis). Ayu 2011;32:478–82. https://doi.org/10.4103/0974-8520.96119.Search in Google Scholar

6. Kimmatkar, N, Thawani, V, Hingorani, L, Khiyani, R. Efficacy and tolerability of Boswellia serrata extract in treatment of osteoarthritis of knee--a randomized double blind placebo controlled trial. Phytomedicine 2003;10:3–7. https://doi.org/10.1078/094471103321648593.Search in Google Scholar

7. Prabhavathi, K, Chandra, US, Soanker, R, Rani, PU. A randomized, double blind, placebo controlled, cross over study to evaluate the analgesic activity of Boswellia serrata in healthy volunteers using mechanical pain model. Indian J Pharmacol 2014;46:475–9. https://doi.org/10.4103/0253-7613.140570.Search in Google Scholar

8. Abdel-Tawab, M, Werz, O, Schubert-Zsilavecz, M. Boswellia serrata: an overall assessment of in vitro, preclinical, pharmacokinetic and clinical data. Clin Pharmacokinet 2011;50:349–69. https://doi.org/10.2165/11586800-000000000-00000.Search in Google Scholar

9. Skarke, C, Kuczka, K, Tausch, L, Werz, O, Rossmanith, T, Barrett, JS, et al.. Increased bioavailability of 11-keto-β-boswellic acid following single oral dose frankincense extract administration after a standardized meal in healthy volunteers: modeling and simulation considerations for evaluating drug exposures. J Clin Pharmacol 2012;52:1592–600. https://doi.org/10.1177/0091270011422811.Search in Google Scholar

10. Hüsch, J, Bohnet, J, Fricker, G, Skarke, C, Artaria, C, Appendino, G, et al.. Enhanced absorption of boswellic acids by a lecithin delivery form (Phytosome®) of Boswellia extract. Fitoterapia 2013;83:89–98. https://doi.org/10.1016/j.fitote.2012.10.002.Search in Google Scholar

11. Buechele, B, Simmer, T. Analysis of 12 different pentacyclic triterpeneic acids from frankincense in human plasma by high performance liquid chromatography and photodiode array detection. J Chromatogr B 2003;795:355–62. https://doi.org/10.1016/s1570-0232(03)00555-5.Search in Google Scholar

12. Sterk, V, Buechele, B, Simmer, T. Effect of food intake on the bioavailability of boswellic acids from herbal preparation in healthy volunteers. Planta Med 2004;70:1155–60. https://doi.org/10.1055/s-2004-835844.Search in Google Scholar

13. Tawab, MA, Kaunzinger, A, Bahr, U, Karas, M, Wurglics, M, Schubert-Zsilavecz, M. Development of a high performance liquid chromatographic method for the determination of 11-keto-beta-boswellic acid in human plasma. J Chromatogr B Biomed Sci 2001;761:221–7. https://doi.org/10.1016/s0378-4347(01)00335-8.Search in Google Scholar

14. Tauch, L, Henkel, A, Siemoneit, U, Poeckel, D, Kather, N, Franke, L, et al.. Identification of human cathespin G as a functional target of boswellic acid from the anti-inflammatory remedy frankincense. J Immunol 2009;183:3433–42. https://doi.org/10.4049/jimmunol.0803574.Search in Google Scholar

15. Sharma, S, Thawani, V, Hingorani, L, Shrivastava, M, Bhate, V, Khiyani, R. Pharmacokinetic study of 11-keto-beta-boswellic acid. Phytomedicine 2004;11:255–60. https://doi.org/10.1078/0944-7113-00290.Search in Google Scholar

16. Gerbeth, K, Meins, J, Kirste, S, Momm, F, Schubert-Zsilavecz, M, Abdel-Tawab, M. Determination of major boswellic acids in plasma by high-pressure liquid chromatography/mass spectrometry. J Pharmaceut Biomed Anal 2011;56:998–1005. https://doi.org/10.1016/j.jpba.2011.07.026.Search in Google Scholar

17. Reising, K, Meins, J, Bastian, B, Eckert, G, Mueller, WE, Schubert-Zsilavecz, M, et al.. Determination of boswellic acids in brain and plasma by high-performance liquid chromatography/tandem mass spectrometry. Anal Chem 2005;77:6640–5. https://doi.org/10.1021/ac0506478.Search in Google Scholar

18. Kruger, P, Daneshfar, R, Eckert, GP, Klein, J, Volmer, D, Bahr, U, et al.. Metabolism of boswellic acids in vitro and in vivo. Drug Metab Dispos 2008;36:1135–42. https://doi.org/10.1124/dmd.107.018424.Search in Google Scholar

19. Kruger, P, Kanzer, J, Hummel, J, Fricker, G, Schubert-Zsilavecz, M, Abdel-Tawab, M. Permeation of boswellia extract in the caco-2 model and possible interaction of its constituents KBA and AKBA with OATPIB3 and MRP2. Eur J Pharmaceut Sci 2009;36:275–84. https://doi.org/10.1016/j.ejps.2008.10.005.Search in Google Scholar

Received: 2020-12-18
Accepted: 2021-01-24
Published Online: 2021-04-05

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