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Tadalafil oral disintegrating tablets: an approach to enhance tadalafil dissolution

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Abstract

Improvement of the dissolution behavior of poorly water soluble tadalafil using solid dispersion technique was investigated. Polyvinylpyrollidone (PVP) was used to prepare solid dispersions (SDs) based on different ratios; 1:1 (SD1,), 1:2 (SD2,), 1:3 (SD3), 1:4 (SD4,) respectively. Tadalafil/PVP/Avicel® in a ratio of 1:2:2 respectively (SD5) was also prepared. SD5 was selected to formulate orally disintegrating tablets (ODTs). Five formulae were prepared (F1–F5) and characterized with respect to drug content uniformity, breaking strength, % friability, wetting behavior, oral disintegration time. Results revealed that SD2 exhibited the highest dissolution rate improvement, where mean dissolution time was 8.22 min compared to 60.12 min for free tadalafil. X-ray powder diffraction spectroscopy and differential scanning calorimetry showed partial drug amorphization in the tested SDs sample which was further confirmed by scanning electron microscope. Moreover, particle size analysis showed the presence of nanocrystals combined with microcrystals dispersed in the prepared SDs. Among the studied solid SDs, SD2 showed the most satisfactory results. In order to improve % yield of SD2 (70.14 %), avicel® was added and the resulting tertiary combination (SD5) showed better flow and higher % yield value (94.22 %). % tadalfil released from SD2 & SD5 differ insignificantly (p ≥ 0.05). F3 (48 % mannitol, 16 % avicel®, 16 % croscarmellose) showed superior wetting time (30.1 s), excellent oral disintegration time (20 s) with an accepted hardness (3.6 kg) & % friability (0.7). Additionally, F3 exhibited a significant improvement of tadalafil dissolution compared to that of pure drug and test commercial tablet brand (p ≤ 0.05).

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References

  • Ahmed AA, Rania HF (2012) A pilot human pharmacokinetic study and influence of formulation factors on orodispersible tablet incorporating meloxicam solid dispersion using factorial design. Pharm Dev Technol 17(1):1–14

    Article  Google Scholar 

  • Ahuja N, Katare OP, Singh B (2007) Studies on dissolution enhancement and mathematical modeling of drug release of a poorly water-soluble drug using water soluble carriers. Eur J Pharm Biopharm 65:26–38

    Article  CAS  PubMed  Google Scholar 

  • Anant P, Anshuman AA et al (2004) Characterization of curcumin–PVP solid dispersion obtained by spray drying. Int J Pharm 271:281–286

    Article  Google Scholar 

  • Anupama K, Shelly K, Neena B (2009) Formulation and evaluation of mouth dissolving tablets of oxcarbazepine. Int J Pharm Pharm Sci 1(1):12–23

    Google Scholar 

  • Badr-Eldin SM, Elkheshen SA, Ghorab MM (2008) Inclusion complexes of tadalafil with natural and chemically modified betacyclodextrin. I: preparation and in vitro evaluation. Eur J Pharm Biopharm 70:819–827

    Article  CAS  PubMed  Google Scholar 

  • Bandari S, Mittapalli RK, Gannu R, Rao YM (2008) Orodispersible tablets: an overview. Asian J Pharm 2(1):2–11

    Article  Google Scholar 

  • Bhaskar C, Shyam S, Anant P (2005) Preparation and evaluation of glibenclamide-polyglycolized glycerides solid dispersions with silicon dioxide by spray drying technique. Eur J Pharm Sci 26(2):219–230

    Article  Google Scholar 

  • Carson CC (2007) Phosphodiesterase type 5 inhibitors: State of the therapeutic class. Urol Clin N Am 34:507–515

    Article  Google Scholar 

  • Chavda HV, Patel CN, Anand IS (2010) Biopharmaceutics classification system. Syst Rev Pharm 1:62–69

    Article  CAS  Google Scholar 

  • Chiou WL, Riegelman S (1971) Pharmaceutical applications of solid dispersion systems. J Pharm Sci 60:1281–1302

    Article  CAS  PubMed  Google Scholar 

  • Duncan QMC (2002) The mechanisms of drug release from solid dispersions in water-soluble polymers. Int J Pharm 231(2):131–144

    Article  Google Scholar 

  • Giammusso B (2008) Daily tadalafil: efficacy and safety of a new dosing regimen. Sexologies 17(1):S19

    Article  Google Scholar 

  • Guidance for Industry Orally Disintegrating Tablets, December (2008) US Department of Health and Human Services, Food Drug and Administration (FDA), Center for Drug Evaluation and Research (CDER): 1–3

  • Higuchi J, Connors K (1965) Phase solubility technique. Adv Anal Chem Instrum 4:117–212

    CAS  Google Scholar 

  • http://www.brenntagspecialties.com/en/pages/Markets_IndustriesServed/Ceramics/Polymers/index.html/PVP_Brochure.pdf

  • http://www.centerwatch.com/drug-information/fda-approved-drugs/drug/1024/adcirca-tadalafil

  • Matthias O, Francois G, Vincenzo M et al (2012) Monotherapy with tadalafil or tamsulosin similarly improved lower urinary tract symptoms suggestive of benign prostatic hyperplasia in an international, randomised, parallel placebo-controlled clinical trial. Eur Urol 61(5):917–925

    Article  Google Scholar 

  • Mohammed MM, Adel MM, Magda WS (2011) Tadalafil inclusion in microporous silica as effective dissolution enhancer: optimization of loading procedure and molecular state characterization. J Pharm Sci 100:1805–1818

    Article  Google Scholar 

  • Pabari RM, Ramtoola Z (2012) Effect of a disintegration mechanism on wetting, water absorption and disintegration time of orodispersible tablets. J Young Pharm 4(3):157–163

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Pandit JK, Khakurel BK (1984) In vitro and in vivo evaluation of some fast release dosage forms of hydrochlorothiazide. Drug Dev Ind Pharm 10(10):1709–1724

    Article  CAS  Google Scholar 

  • Paramita D, Sabyasachi M (2010) Orodispersible tablets: a new trend in drug delivery. J Nat Sci Biol Med 1(1):2–5

    Article  Google Scholar 

  • Patel RP, Patel DJ, Bhimani DB, Patel JK (2008) Physicochemical characterization and dissolution study of solid dispersions of Furosemide with polyethylene glycol 600 and polyvinylpyrollidine K30. Dissolut Technol. 15:17–25

    Article  CAS  Google Scholar 

  • Raymond CR (2008) Handbook of pharmaceutical excipients, 7th edn. APhA Publishers, Washington

    Google Scholar 

  • Sandip S, Mukesh B, Ashish R et al (2013) An overview on the mechanisms of solubility and dissolution rate enhancement in solid dispersion. Int J Pharm Tech Res 5(1):31–39

    Google Scholar 

  • Sarah KB (2005) Guidelines from the international conference on harmonisation (ICH). A review. J Pharm Biomed Anal 38(5):798–805

    Article  Google Scholar 

  • Senem SÖ, İmran V (2009) Advantages and quality control of orally disintegrating tablets. FABAD J Pharm Sci 34(3):167–172

    Google Scholar 

  • Sherimeier S, Schmidt PC (2002) Fast dispersible ibuprofen tablets. Eur J Pharm Sci 15:295–305

    Article  Google Scholar 

  • Takatsuki S, Calderback M, Ivy DD (2012) Initial experience with tadalafil in pediatric pulmonary arterial hypertension. Pediatr Cardiol 33(5):683–688

    Article  PubMed Central  PubMed  Google Scholar 

  • Tansel Ç (2010) Effect of compression speed and lubrication on the compaction properties of some commonly used direct compression materials. Turk J Pharm Sci 7(2):127–138

    Google Scholar 

  • Van den Mootera G, Wuytsa M, Blatonb N et al (2001) Physical stabilisation of amorphous ketoconazole in solid dispersions with polyvinylpyrrolidone K25. Eur J Pharm Sci 12(3):261–269

    Article  Google Scholar 

  • Vikrant V, Pankajkumar S, Poonam K, Manali S, Yogesh P (2009) Physicochemical characterization of solid dispersion systems of tadalafil with poloxamer 407. Acta Pharm 59:453–461

    Google Scholar 

  • Wasfy MO, Al-Sayed AS (2014) Evaluation of tadalafil nanosuspensions and their PEG solid dispersion matrices for enhancing its dissolution properties. AAPS PharmSciTech 15(2):364–374

    Article  Google Scholar 

  • Zhang Y, Law Y, Chakrabarti S (2003) Physical properties and compact analysis of commonly used direct compression binders. AAPS PharmSciTech 4(4):E62

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This article does not contain any studies with human and animal subjects performed by any of the authors. All authors (A. Refaat, M. Sokar, F. Ismail, N. Boraei) declare that they have no conflict of interest.

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Correspondence to Magda Sokar.

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Refaat, A., Sokar, M., Ismail, F. et al. Tadalafil oral disintegrating tablets: an approach to enhance tadalafil dissolution. Journal of Pharmaceutical Investigation 45, 481–491 (2015). https://doi.org/10.1007/s40005-015-0196-x

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  • DOI: https://doi.org/10.1007/s40005-015-0196-x

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