Formulation and In-vitro Characterization of Metformin Hydrochloride-loaded Liposomes


  • Shrouk magdy Pharmaceutics Department, Faculty of Pharmacy, Deraya University, Minia, Egypt
  • Zeinab Fathalla Pharmaceutics Department, Faculty of Pharmacy, Minia University, Minia, Egypt
  • Eman Alaaeldin Pharmaceutics Department, Faculty of Pharmacy, Deraya University, Minia, Egypt
  • Heba F. Mansour Pharmaceutics Department, Faculty of Pharmacy, Minia University, Minia, Egypt


Metformin HCL, Liposome, ex-vivo permeation, skin, Drug formulations, stability study, parameter


The aim of study. is to formulate Metformin hydrochloride-loaded novel liposomal vesicles and investigate their physical stability. A new metformin hydrochloride (Met-HCL) liposomal formulation was prepared  for topical delivery. Traditionally, the biguanide metformin could be categorized the first line in treatment of diabetes. The prepared metformin hydrochloride-loaded liposomal vesicles were investigated  for different in vitro characterisations. Eleven different formulations were developed adopting a thin film hydration method using different molar concentrations of Phospholipon® 90G, cholesterol and metformin hydrochloride. The effect of varying concentrations of Phospholipon® 90G, cholesterol and metformin hydrochloride on entrapment efficiency percent, ex-vivo skin permeation percentage, vesicle size and zeta potential was studied. Metformin-loaded liposome stability over a period of time 90 days was investigated. Results. The optimized metformin hydrochloride liposomes, F2, F6 and F11 were selecte. The selected formulations displayed highly efficient permeation percent via the excised mice skin 53±0.09 %, 30±0.4 % and 40±0.02 % respectively. The formulations showed EE % of  80±0.09 %, 28.6±0.02 % and 71.8±0.4 % respectively. Morphology of F2  liposomal surface revealed spherical three-dimensional structure. The stability study revealed about 10-23 percent drug leaching out of the vesicular liposomes (F2) within 90 days. Conclusion. Metformin hydrochloride-loaded liposomal vesicles can provide a potentially promising and convenient approach for topical delivery.


. Meisner, D. and M. Mezei, Liposome ocular delivery systems. Advanced drug delivery reviews, 1995. 16(1): p. 75-93.

. Gregoriadis, G. and A.T. Florence, Liposomes in drug delivery. Drugs, 1993. 45(1): p. 15-28.

. Sweeney, L.G., et al., Spray-freeze-dried liposomal ciprofloxacin powder for inhaled aerosol drug delivery. International journal of pharmaceutics, 2005. 305(1-2): p. 180-185.

. van Winden, E.C. and D.J. Crommelin, Short term stability of freeze-dried, lyoprotected liposomes. Journal of controlled release, 1999. 58(1): p. 69-86.

. Okada, J.i., S. Cohen, and R. Langer, In vitro evaluation of polymerized liposomes as an oral drug delivery system. Pharmaceutical research, 1995. 12(4): p. 576-582.

. Dong, C. and J. Rogers, Polymer-coated liposomes; stability and release of ASA from carboxymethyl chitin-coated liposomes. Journal of Controlled Release, 1991. 17(3): p. 217-224.

. Werner, C. and A. Wendel, Hepatic uptake and antihepatotoxic properties of vitamin E and liposomes in the mouse. Chemico-biological interactions, 1990. 75(1): p. 83-92.

. Mezei, M., Liposomes a selective drug delivery system for the topical route of administration: gel dosage. J Pharm Pharmacol, 1982. 34: p. 473-474.

. Doppalapudi, S., et al., Psoralen loaded liposomal nanocarriers for improved skin penetration and efficacy of topical PUVA in psoriasis. European journal of pharmaceutical sciences, 2017. 96: p. 515-529.

. Agarwal, R., O. Katare, and S. Vyas, Preparation and in vitro evaluation of liposomal/niosomal delivery systems for antipsoriatic drug dithranol. International journal of pharmaceutics, 2001. 228(1-2): p. 43-52.

. Bennett, W.L., et al., Comparative effectiveness and safety of medications for type 2 diabetes: an update including new drugs and 2-drug combinations. Annals of internal medicine, 2011. 154(9): p. 602-613.

. Inzucchi, S.E., et al., Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Spectrum, 2012. 25(3): p. 154-171.

. Qaseem, A., et al., Oral pharmacologic treatment of type 2 diabetes mellitus: a clinical practice guideline from the American College of Physicians. Annals of internal medicine, 2012. 156(3): p. 218-231.

. Collier, C.A., et al., Metformin counters the insulin-induced suppression of fatty acid oxidation and stimulation of triacylglycerol storage in rodent skeletal muscle. American Journal of Physiology-Endocrinology and Metabolism, 2006. 291(1): p. E182-E189.

. Bailey, C.J., Metformin: historical overview. Diabetologia, 2017. 60(9): p. 1566-1576.

. Shankar, M.B., et al., Estimation of pioglitazone hydrochloride and metformin hydrochloride in tablets by derivative spectrophotometry and liquid chromatographic methods. Journal of AOAC international, 2005. 88(4): p. 1167-1172.

. Mubeen, G. and K. Noor, Spectrophotometric method for analysis of metformin hydrochloride. Indian journal of pharmaceutical sciences, 2009. 71(1): p. 100.

. Arayne, M., et al., Spectrophotometric quantitation of metformin in bulk drug and pharmaceutical formulations using multivariate technique. Indian journal of pharmaceutical sciences, 2009. 71(3): p. 331.

. New, R.R., Preparation of liposomes. Liposomes: a practical approach., 1990: p. 33-104.

. Deamer, D. and A. Bangham, Large volume liposomes by an ether vaporization method. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1976. 443(3): p. 629-634.

. Fueldner, H.H., Characterization of a third phase transition in multilamellar dipalmitoyllecithin liposomes. Biochemistry, 1981. 20(20): p. 5707-5710.

. Mostafa, M., et al., Optimization and characterization of thymoquinone-loaded liposomes with enhanced topical anti-inflammatory Activity. AAPS PharmSciTech, 2018. 19(8): p. 3490-3500.

. Qiu, Y., et al., Enhancement of skin permeation of docetaxel: a novel approach combining microneedle and elastic liposomes. Journal of Controlled Release, 2008. 129(2): p. 144-150.

. Hernández‐Caselles, T., J. Villalain, and J. Gómez‐Fernández, Stability of liposomes on long term storage. Journal of pharmacy and pharmacology, 1990. 42(6): p. 397-400.

. Gruner, S.M., et al., Novel multilayered lipid vesicles: comparison of physical characteristics of multilamellar liposomes and stable plurilamellar vesicles. Biochemistry, 1985. 24(12): p. 2833-2842.

. Armengol, X. and J. Estelrich, Physical stability of different liposome compositions obtained by extrusion method. Journal of microencapsulation, 1995. 12(5): p. 525-535.

. Kesisoglou, F., et al., Liposomal formulations of inflammatory bowel disease drugs: local versus systemic drug delivery in a rat model. Pharmaceutical research, 2005. 22(8): p. 1320-1330.

. Barenholz, Y., Relevancy of drug loading to liposomal formulation therapeutic efficacy. Journal of liposome research, 2003. 13(1): p. 1-8.

. Xu, X., M.A. Khan, and D.J. Burgess, A quality by design (QbD) case study on liposomes containing hydrophilic API: I. Formulation, processing design and risk assessment. International journal of pharmaceutics, 2011. 419(1-2): p. 52-59.

. Mokhtar, M., et al., Effect of some formulation parameters on flurbiprofen encapsulation and release rates of niosomes prepared from proniosomes. International journal of pharmaceutics, 2008. 361(1-2): p. 104-111.

. Pons, M., M. Foradada, and J. Estelrich, Liposomes obtained by the ethanol injection method. International journal of pharmaceutics, 1993. 95(1-3): p. 51-56.

. Elsayed, M.M., et al., Deformable liposomes and ethosomes: mechanism of enhanced skin delivery. International journal of pharmaceutics, 2006. 322(1-2): p. 60-66.

. Kimelberg, H.K., E.G. Mayhew, and G. Gregoriadis, Properties and biological effects of liposomes and their uses in pharmacology and toxicology. CRC Critical Reviews in Toxicology, 1978. 6(1): p. 25-79.

. Jaafar-Maalej, C., et al., Ethanol injection method for hydrophilic and lipophilic drug-loaded liposome preparation. Journal of liposome research, 2010. 20(3): p. 228-243.

. Harashima, H., et al., Enhanced hepatic uptake of liposomes through complement activation depending on the size of liposomes. Pharmaceutical research, 1994. 11(3): p. 402-406.

. Batzri, S. and E.D. Korn, Single bilayer liposomes prepared without sonication. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1973. 298(4): p. 1015-1019.

. Szoka, J.F., The future of liposomal drug delivery. Biotechnology and applied biochemistry, 1990. 12(5): p. 496-500.

. Fatouros, D., et al., Preparation and properties of arsonolipid containing liposomes. Chemistry and physics of lipids, 2001. 109(1): p. 75-89.

. Klein, R., The detection of oxidation in liposome preparations. Biochimica et Biophysica Acta (BBA)-Lipids and Lipid Metabolism, 1970. 210(3): p. 486-489.

. Olson, F., et al., Preparation of liposomes of defined size distribution by extrusion through polycarbonate membranes. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1979. 557(1): p. 9-23.

. Frisken, B., C. Asman, and P. Patty, Studies of vesicle extrusion. Langmuir, 2000. 16(3): p. 928-933.

. Nayar, R., M.J. Hope, and P.R. Cullis, Generation of large unilamellar vesicles from long-chain saturated phosphatidylcholines by extrusion technique. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1989. 986(2): p. 200-206.

. Martin, F.J. and J.K. Morano, Liposome extrusion method. 1988, Google Patents.

. Vargha-Butler, E. and E. Hurst, Study of liposomal drug delivery systems 1. Surface characterization of steroid loaded MLV liposomes. Colloids and Surfaces B: Biointerfaces, 1995. 3(5): p. 287-295.

. Jones, M.N., The surface properties of phospholipid liposome systems and their characterisation. Advances in colloid and interface science, 1995. 54: p. 93-128.

. Jones, M.N., Surface properties and interactions of vesicles. Current Opinion in Colloid & Interface Science, 1996. 1(1): p. 91-100.

. Sharma, A. and U.S. Sharma, Liposomes in drug delivery: progress and limitations. International journal of pharmaceutics, 1997. 154(2): p. 123-140.

. Sharma, A., E. Mayhew, and R.M. Straubinger, Antitumor effect of taxol-containing liposomes in a taxol-resistant murine tumor model. Cancer research, 1993. 53(24): p. 5877-5881.

. Padamwar, M.N. and V.B. Pokharkar, Development of vitamin loaded topical liposomal formulation using factorial design approach: drug deposition and stability. International journal of pharmaceutics, 2006. 320(1-2): p. 37-44.




How to Cite

magdy, S. ., Fathalla, Z. ., Alaaeldin, E. ., & F. Mansour, H. . (2021). Formulation and In-vitro Characterization of Metformin Hydrochloride-loaded Liposomes. International Journal of Sciences: Basic and Applied Research (IJSBAR), 56(1), 150–164. Retrieved from