Main Article Content

Ms Priya Sharma
Dr Amarjeet Singh
Dr Navjot Singh Sethi


Berberine HCl, Diabetes Mellitus, Permeation enhancer, Quality by design, Phospholipid complex


Aim: To design and development of optimized berberine chloride formulation by using the phospholipid complexation and permeation enhancer for the treatment of diabetes.

Material and methods: The phospholipid complex was prepared by solvent evaporation method using the soya lecithin, Phospholipid 90G and lipoid S 100. The prepared phospholipid complex was evaluated for the physical appearance, FTIR, percentage of drug complexing efficiency, total drug content and percentage drug loading and in-vitro permeation study. The berberine loaded phospholipid complex using phenyl piperazine and methyl piperazine were used as permeation enhancer. The formulated complex was evaluated physical appearance, pH, FTIR, drug content, permeability study, In-vitro permeation study, stability study and In-vivo pharmacokinetic study.

Results: The preformulation study of Berberine HCl involved investigating various parameters such as organoleptic properties, melting point, partition coefficient, solubility, and absorption maxima. Berberine HCl exhibited a yellow color with a bitter taste, a melting point, partition coefficient. Solubility testing revealed its sparing solubility in methanol and slight solubility in ethanol, water, and phosphate buffer pH 6.8. FTIR analysis confirmed the presence of characteristic functional groups in Berberine HCl. Furthermore, the formation of a complex with phospholipids was indicated by shifts in characteristic peaks. Physical appearance assessments of the berberine HCl-phospholipid complex formulations showed a consistent yellow color. Percentage drug complexation ranged from 56.098% to 80.466%, with solubility in n-octanol and water varying across formulations. In vitro permeability studies demonstrated enhanced berberine HCl permeation from the complexed formulations, notably DBPC14. The stability study indicated no significant changes in physical appearance or drug content over three months. In-vivo pharmacokinetic analysis revealed improved bioavailability and absorption of berberine HCl from the phospholipid complex DBPC14 compared to the pure drug and a mixture with phenyl piperazine. These findings suggest the potential of berberine HCl-phospholipid complexes for enhanced therapeutic outcomes in the treatment of metabolic disorders such as diabetes mellitus.

Conclusion: From the present study, it can be concluded that the importance of optimization of formulation development using quality by design strategy to achieve phospholipid with consistent quality.

Abstract 240 | PDF Downloads 24


Ai, Xiaopeng, Peiling Yu, Liuling Luo, and Xianli Meng. 2021. “Berberine: A Review of Its Pharmacokinetics Properties and Therapeutic Potentials in Diverse Vascular Diseases.” Frontiers in Pharmacology 12: 762654.
2. AM Fiorentino, Flavia, and Herida RN Salgado. 2012. “Development and Validation of a UV-Spectrophotometric Method for Determination of Flucloxacillin Sodium in Capsules.” Current Pharmaceutical Analysis 8(1): 101–6.
3. Amiri, Hoda et al. 2018. “Response Surface Methodology Modeling to Improve Degradation of Chlorpyrifos in Agriculture Runoff Using TiO2 Solar Photocatalytic in a Raceway Pond Reactor.” Ecotoxicology and environmental safety 147: 919–25.
4. Atlas, Diabetes. 2015. “International Diabetes Federation.” IDF Diabetes Atlas, 7th edn. Brussels, Belgium: International Diabetes Federation 33(2).
5. Battu, Sunil Kumar et al. 2010. “Physicochemical Characterization of Berberine Chloride: A Perspective in the Development of a Solution Dosage Form for Oral Delivery.” Aaps Pharmscitech 11: 1466–75.
6. Bhavyasri, K, T Surekha, and D Rambabu. 2019. “Bioanalytical Method Development and Validation of Atorvastatin in Human Plasma by Using UV-Visibile Spectrophotometry.” Journal of Pharmaceutical Sciences and Research 11(6): 2243–46.
7. Comincini, Sergio et al. 2023. “Development of Berberine-Loaded Nanoparticles for Astrocytoma Cells Administration and Photodynamic Therapy Stimulation.” Pharmaceutics 15(4): 1078.
8. Dora, Chander Parkash et al. 2017. “Improved Metabolic Stability and Therapeutic Efficacy of a Novel Molecular Gemcitabine Phospholipid Complex.” International journal of pharmaceutics 530(1–2): 113–27.
9. Dudhipala, Narendar, and Kishan Veerabrahma. 2015. “Pharmacokinetic and Pharmacodynamic Studies of Nisoldipine-Loaded Solid Lipid Nanoparticles Developed by Central Composite Design.” Drug development and industrial pharmacy 41(12): 1968–77.
10. Elsheikh, Manal A, Yosra S R Elnaggar, Dalia A Hamdy, and Ossama Y Abdallah. 2018. “Novel Cremochylomicrons for Improved Oral Bioavailability of the Antineoplastic Phytomedicine Berberine Chloride: Optimization and Pharmacokinetics.” International journal of pharmaceutics 535(1–2): 316–24.
11. ENV, D. 2012. “Joint Meeting of the Chemicals Committee and the Working Party on Chemicals, Pesticides and Biotechnology.” Brussels: Directorate General Environment of the European Commission.
12. Fein, Katherine C, John P Gleeson, Alexandra N Newby, and Kathryn A Whitehead. 2022. “Intestinal Permeation Enhancers Enable Oral Delivery of Macromolecules up to 70 KDa in Size.” European Journal of Pharmaceutics and Biopharmaceutics 170: 70–76.
13. Feng, Jin et al. 2010. “Simultaneous Determination of Baicalin, Baicalein, Wogonin, Berberine, Palmatine and Jatrorrhizine in Rat Plasma by Liquid Chromatography–Tandem Mass Spectrometry and Application in Pharmacokinetic Studies after Oral Administration of Traditional Chinese .” Journal of pharmaceutical and biomedical analysis 53(3): 591–98.
14. Freag, May S, Wedad M Saleh, and Ossama Y Abdallah. 2018. “Self-Assembled Phospholipid-Based Phytosomal Nanocarriers as Promising Platforms for Improving Oral Bioavailability of the Anticancer Celastrol.” International journal of pharmaceutics 535(1–2): 18–26.
15. Gonzalez-Mira, E et al. 2010. “Optimizing Flurbiprofen-Loaded NLC by Central Composite Factorial Design for Ocular Delivery.” Nanotechnology 22(4): 45101.
16. Guihua, H et al. 2005. “Preparation and Solubility of Breviscapine Phospholipid Complex.” Chin. J. Pharm. 36: 84–86.
17. Ich, I C H. 2005. “Topic Q2 (R1) Validation of Analytical Procedures: Text and Methodology.” In Int. Conf. Harmon, , 17.
18. Kabary, Dalia M et al. 2018. “Hyaluronate/Lactoferrin Layer-by-Layer-Coated Lipid Nanocarriers for Targeted Co-Delivery of Rapamycin and Berberine to Lung Carcinoma.” Colloids and Surfaces B: Biointerfaces 169: 183–94.
19. Kasim, Nehal A et al. 2004. “Molecular Properties of WHO Essential Drugs and Provisional Biopharmaceutical Classification.” Molecular pharmaceutics 1(1): 85–96.
20. Khatik, Renuka et al. 2016. “Development, Characterization and Toxicological Evaluations of Phospholipids Complexes of Curcumin for Effective Drug Delivery in Cancer Chemotherapy.” Drug delivery 23(3): 1057–68.
21. Koide, T et al. 2001. “Berberine Hydrochloride Reference Standard (Control 001) of National Institute of Health Sciences.” Kokuritsu Iyakuhin Shokuhin Eisei Kenkyujo Hokoku= Bulletin of National Institute of Health Sciences (119): 97–100.
22. Laid, Tedjani Mohammed, Khelef Abdelhamid, Laouini Salah Eddine, and Bouafia Abderrhmane. 2021. “Optimizing the Biosynthesis Parameters of Iron Oxide Nanoparticles Using Central Composite Design.” Journal of Molecular Structure 1229: 129497.
23. Li, Pengfei et al. 2020. “Preparation and Adsorption Characteristics of Rosin-Based Polymer Microspheres for Berberine Hydrochloride and Separation of Total Alkaloids from Coptidis Rhizoma.” Chemical Engineering Journal 392: 123707.
24. Liu, Chang-Shun, Yu-Rong Zheng, Ying-Feng Zhang, and Xiao-Ying Long. 2016. “Research Progress on Berberine with a Special Focus on Its Oral Bioavailability.” Fitoterapia 109: 274–82.
25. Lu, Yan, Yu Zhang, Ziyi Yang, and Xing Tang. 2009. “Formulation of an Intravenous Emulsion Loaded with a Clarithromycin–Phospholipid Complex and Its Pharmacokinetics in Rats.” International journal of pharmaceutics 366(1–2): 160–69.
26. Maiti, Kuntal et al. 2007. “Curcumin–Phospholipid Complex: Preparation, Therapeutic Evaluation and Pharmacokinetic Study in Rats.” International journal of pharmaceutics 330(1–2): 155–63.
27. Mendez, Andreas S L, Martin Steppe, and Elfrides E S Schapoval. 2003. “Validation of HPLC and UV Spectrophotometric Methods for the Determination of Meropenem in Pharmaceutical Dosage Form.” Journal of pharmaceutical and biomedical analysis 33(5): 947–54.
28. Peng, Qiang et al. 2012. “A Rapid-Acting, Long-Acting Insulin Formulation Based on a Phospholipid Complex Loaded PHBHHx Nanoparticles.” Biomaterials 33(5): 1583–88.
29. Pu, Yiqiong et al. 2016. “20 (S)-Protopanaxadiol Phospholipid Complex: Process Optimization, Characterization, in Vitro Dissolution and Molecular Docking Studies.” Molecules 21(10): 1396.
30. Selzer, Dominik et al. 2013. “Finite and Infinite Dosing: Difficulties in Measurements, Evaluations and Predictions.” Advanced drug delivery reviews 65(2): 278–94.
31. Shah, Punit P et al. 2014. “Effect of Combination of Hydrophilic and Lipophilic Permeation Enhancers on the Skin Permeation of Kahalalide F.” Journal of Pharmacy and Pharmacology 66(6): 760–68.
32. Srikanth, Meka Venkata et al. 2012. “Statistical Design and Evaluation of a Propranolol HCl Gastric Floating Tablet.” Acta Pharmaceutica Sinica B 2(1): 60–69.
33. Stuettgen, Vivien, and David James Brayden. 2020. “Investigations of Piperazine Derivatives as Intestinal Permeation Enhancers in Isolated Rat Intestinal Tissue Mucosae.” The AAPS Journal 22: 1–13.
34. Thumma, Sridhar et al. 2008. “Preformulation Studies of a Prodrug of Δ 9-Tetrahydrocannabinol.” AAPS PharmSciTech 9: 982–90.
35. Varshosaz, Jaleh et al. 2010. “Development and Optimization of Solid Lipid Nanoparticles of Amikacin by Central Composite Design.” Journal of liposome research 20(2): 97–104.
36. Wang, Zhijun, Jeffrey Wang, and Patrick Chan. 2013. “Treating Type 2 Diabetes Mellitus with Traditional Chinese and Indian Medicinal Herbs.” Evidence-Based Complementary and Alternative Medicine 2013.
37. Xie, Weidong, Yunan Zhao, and Yaou Zhang. 2011. “Traditional Chinese Medicines in Treatment of Patients with Type 2 Diabetes Mellitus.” Evidence-Based Complementary and Alternative Medicine 2011.
38. Yanyu, Xiao, Song Yunmei, Chen Zhipeng, and Ping Qineng. 2006. “The Preparation of Silybin–Phospholipid Complex and the Study on Its Pharmacokinetics in Rats.” International journal of pharmaceutics 307(1): 77–82.
39. Yasir, Mohd et al. 2021. “Buspirone Loaded Solid Lipid Nanoparticles for Amplification of Nose to Brain Efficacy: Formulation Development, Optimization by Box-Behnken Design, in-Vitro Characterization and in-Vivo Biological Evaluation.” Journal of Drug Delivery Science and Technology 61: 102164.
40. Yu, Fei et al. 2016. “Monodisperse Microparticles Loaded with the Self-Assembled Berberine-Phospholipid Complex-Based Phytosomes for Improving Oral Bioavailability and Enhancing Hypoglycemic Efficiency.” European Journal of Pharmaceutics and Biopharmaceutics 103: 136–48.
41. ———. 2017. “PEG–Lipid–PLGA Hybrid Nanoparticles Loaded with Berberine–Phospholipid Complex to Facilitate the Oral Delivery Efficiency.” Drug delivery 24(1): 825–33.
42. Zhang, Zhenhai et al. 2014. “Solid Dispersion of Berberine–Phospholipid Complex/TPGS 1000/SiO2: Preparation, Characterization and in Vivo Studies.” International journal of pharmaceutics 465(1–2): 306–16.
43. Zhu, Jia-Xiao et al. 2013. “Development of Self-Microemulsifying Drug Delivery System for Oral Bioavailability Enhancement of Berberine Hydrochloride.” Drug Development and Industrial Pharmacy 39(3): 499–506.
44. Zimmet, Paul, KGMM Alberti, and Jonathan Shaw. 2001. “Global and Societal Implications of the Diabetes Epidemic.” Nature 414(6865): 782–87.