FORMULATION DEVELOPMENT OF IMMEDIATE RELEASE PELLETS OF TADALAFIL: SOLIDIFICATION APPROACH FOR NANOSUSPENSION

SOLIDIFICATION APPROACH FOR NANOSUSPENSION

  • SHOBHA UBGADE Gurunanak College of Pharmacy, Dixit Nagar, Nagpur, India
  • VAISHALI KILOR Gurunanak College of Pharmacy, Dixit Nagar, Nagpur, India
  • VIDYA BAHEKAR Gurunanak College of Pharmacy, Dixit Nagar, Nagpur, India
  • ABHAY ITTADWAR Gurunanak College of Pharmacy, Dixit Nagar, Nagpur, India

Abstract

Objective: Nanosuspension is known to enhance the saturation solubility and dissolution velocity of poorly soluble drugs owing to the increased surface area of nanosized particles. Stability of these solubility enhancing systems can be improved by converting them into solidified forms. To simultaneously achieve enhanced dissolution and improved stability, an attempt has been made to increase the dissolution rate of poorly soluble drug tadalafil by formulating immediate release pellets of its nanosuspension.


Methods: Tadalafil nanosuspensions were prepared using high shear homogenization technique and hydroxypropyl methylcellulose (HPMC) E 15, sodium dodecyl sulphate (SDS) as stabilizers. Prepared nanosuspensions were subjected to the characterization of particle size distribution, zeta potential, drug loading and saturation solubility. Optimized nanosuspension was solidified by preparing immediate release pellets: for improved stability, where tadalafil nanosuspension was used as a binder. Pellets were prepared by extrusion-spheronization technique using κ-carrageenan as a pelletizing aid.


Results: Prepared immediate release pellets disintegrated within 03 min. In vitro dissolution studies showed 85% drug release within 45 min in pH 1.2 buffer from immediate release pellets containing tadalafil nanosuspension.


Conclusion: It can be concluded that formulation of nanosuspension of poorly soluble drug and its use as a binder for the preparation of immediate release pellets markedly improved the dissolution rate.

Keywords: Tadalafil, Nanosuspension, Immediate release, Dissolution enhancement, Solidification

References

1. Javiana L, Teobaldo A, Jacqueline S, Hernandez L, Von Plessing C. Preliminary pharmacokinetic study of different preparations of acyclovir with b-cyclodextrin. J Pharm Sci 2002;91:2593–8.
2. Norbert R, Muller BW. Dissolution rate enhancement by in situ micronization of poorly water-soluble drugs. Pharm Res 2002;19:1894–900.
3. Hajare AA, Jadhav PR. Improvement of solubility and dissolution rate of indomethacin by solid dispersion in polyvinyl pyrrolidone K30 and poloxomer 188. Asian J Pharm Technol 2012;2:116–22.
4. Stella VJ, He Q. Cyclodextrins. Toxicol Pathol 2008;36:30–42.
5. Asare Addo K, Supuk E, Al Hamidi H, Owusu Ware S, Nokhodchi A, Conway BR. Triboelectrification and dissolution property enhancements of solid dispersions. Int J Pharm 2015;485:306–16.
6. Laxmi P, Ashwinikumar G. Nanosuspension technology: a review. Int J Pharm Pharm Sci 2010;(2, Suppl 4):35-40.
7. Baek I, Kim J, Eun Sol Ha, Gwang Ho Choo. Dissolution and oral absorption of pranlukast nanosuspensions stabilized by hydroxypropylmethylcellulose. Int J Biol Macromol 2014;67:53-7.
8. Van Eerdenbrugh B, Froyen L, Van Humbeeck J, Martens JA, Augustijns P, Van den Mooter G. Drying of crystalline drug nanosuspensions-The importance of surface hydrophobicity on dissolution behavior upon redispersion. Eur J Pharm Sci 2008;35:127–35.
9. He W, Lu Y, Qi J, Chen L, Yin L, Wu W. Formulating food protein-stabilized indomethacin nanosuspensions into pellets by fluid-bed coating technology: physical characterization, redispersibility, and dissolution. Int J Nanomed 2013;8:3119–28.
10. Singare DS, Marella S, Gowthamrajan K, Kulkarni GT, Vooturi R, Rao PS. Optimization of formulation and process variable of nanosuspension: an industrial perspective. Int J Pharm 2010;402:213–20
11. Ghebre Sellassie. Pharmaceutical pelletization technology. New York: Marcel Dekker; 1989.
12. Nassab PR, Rajko R, Szabo Revesz P. Physicochemical characterization of meloxicam–mannitol binary systems. J Pharm Biomed Anal 2006;41:1191–7.
13. Thommes M, Kleinebudde P. Use of ?-carrageenan as alternative pelletization aid to microcrystalline cellulose in extrusion/spheronization, I: influence of type and fraction of filler. Eur J Pharm Biopharm 2006;63:59–67.
14. Brock GB, McMahon CG, Chen KK, Costigan T, Shen W, Watkins V. Efficacy and safety of tadalafil for the treatment of erectile dysfunction: results of integrated analyses. J Urol 2002;168:1332–6.
15. Kilor V, Sapkal N, Daud A, Humne S, Gupta T. Development of stable nanosuspension loaded oral films of glimepiride with improved bioavailability. Int J Appl Pharm 2017;9 Suppl 2:28-33.
16. Patravale VB, Date AA, Kulkarni RN. Nanosuspensions: a promising drug delivery strategy. J Pharm Pharmacol 2004;56 Suppl 7:827–40.
17. Kilor VA, Sapkal NP, Awari JG, Shewale BP. Development and characterization of enteric-coated immediate-release pellets of aceclofenac by extrusion/spheronization technique using ?-carrageenan as a pelletizing agent. AAPS PharmSciTech 2010;11 Suppl 1:336–43.
18. Lee J, Lee SJ, Choi JY, Yoo JY, Ahn CH. Amphiphilic amino acid copolymers as stabilizers for the preparation of nanocrystal dispersion. Eur J Pharm Sci 2005;24:441–9.
19. Bilgili E, Li M, Afolabi A. Is the combination of cellulosic polymers and anionic surfactants a good strategy for ensuring physical stability of BCS Class II drug nanosuspensions? Pharm Dev Technol 2016;21 Suppl 4:499–510.
20. Muller RH, Jacobs C, Kayser O. Nanosuspensions as particulate drug formulations in therapy: rationale for the development and what we can expect for the future. Adv Drug Delivery Rev 2001;47:3-19.
21. Thommes M, Kleinebudde P. Use of ?-carrageenan as alternative pelletization aid to microcrystalline cellulose in extrusion/spheronization, II: influence of drug and filler type. Eur J Pharm Biopharm 2006;63:68–75.
Statistics
59 Views | 102 Downloads
Citatons
How to Cite
UBGADE, S., KILOR, V., BAHEKAR, V., & ITTADWAR, A. (2019). FORMULATION DEVELOPMENT OF IMMEDIATE RELEASE PELLETS OF TADALAFIL: SOLIDIFICATION APPROACH FOR NANOSUSPENSION. International Journal of Applied Pharmaceutics, 11(4), 124-131. https://doi.org/10.22159/ijap.2019v11i4.32331
Section
Original Article(s)