Journal of Pharmaceutical Investigation

, Volume 45, Issue 1, pp 91–99 | Cite as

Hydroxy propyl β-cyclodextrin complexation of promethazine hydrochloride for the formulation of fast dissolving sublingual film: in vitro and in vivo evaluation

  • Jigar N. ShahEmail author
  • Kashyap N. Shah
  • Tejal A. Mehta
Research Article


Promethazine hydrochloride (PMZ-HCl) is a classical anti-motion sickness drug which has oral bioavailability (25 %) due to extensive hepatic first pass metabolism. To overcome this drawback, novel, fast dissolving sublingual film (FDSF) of drug was developed. FDSF was formulated using pullulan and propylene glycol (PG) by solvent casting method. Complete taste masking was successfully obtained with HP β-CD, aspartame and grape fruit flavour. Complex of drug was proved using Fourier transfer infrared spectroscopy, differential scanning calorimetry and X-ray diffraction studies. Optimization of concentration of pullulan and PG was done using 32 full factorial design. Batches were evaluated for the parameters like elongation, tensile strength, folding endurance and in vitro disintegration studies. In vitro dissolution indicated 100 % drug release within 7.5 min. Environmental scanning electron microscopy studies also showed uniform drug distribution and integrity of film. In vivo sublingual absorption in human indicated that 70 % of drug absorbed in 10 min. The stability studies indicated that label should state “Store at cool, dry place” at temperature 25 °C. So by formulating the taste masked FDSF of PMZ-HCl will give faster onset of action and avoid unnecessary drug intake leading to traveller friendly formulation.


Promethazine hydrochloride Fast dissolving sublingual film Pullulan Hydroxy propyl β-cyclodextrin In vivo sublingual studies in human 



These authors, J. N.Shah, K. Shah, T.A. Mehta, declare that they have no conflict of interest.


  1. Aditya D, Mangal N (2008) Formulation and evaluation of fast dissolving films for delivery of triclosan to the oral cavity. AAPS PharmSciTech 9(2):349–355CrossRefGoogle Scholar
  2. Artusi M, Santi P, Colombo P, Junginger HE (2003) Buccal delivery of thiocolchicoside: in vitro and in vivo permeation studies. Int J Pharm 250(1):203–213CrossRefPubMedGoogle Scholar
  3. Ashok RP, Pradeep RV (2009) Preparation and evaluation of taste masked famotidine formulation using drug/β-cyclodextrin/polymer ternary complexation approach. AAPS PharmSciTech 10:544–550Google Scholar
  4. Basani G, Subash V, Guru S, Madhusudan R (2010) Overview on fast dissolving films. Int J Pharm Pharm Sci 2(3):29–33Google Scholar
  5. Chang RK, Guo X, Burnside BA, Couch RA (2000) Fast dissolving tablets. Pharm Tech 24:52–58Google Scholar
  6. Choudhary DR, Patel VA, Chhalotiya UK, Patel HV, Kundawala AJ (2012) Natural polysaccharides as film former: a feasibility study for development of rapid dissolving films of ondansetron hydrochloride. Int J Pharm Pharm Sci 4(3):78–85Google Scholar
  7. Cilurzo F, Cupone IE, Minghetti P, Burrati S, Gennari CG, Montanari L (2011) Diclofenac fast-dissolving film: suppression of bitterness by taste a sensing system. Drug Dev Ind Pharm 37(3):252–259CrossRefPubMedGoogle Scholar
  8. Dahiya M, Sumit SA (2009) A review on mouth dissolving films. Curr Drug Deliv 6:469–476CrossRefPubMedGoogle Scholar
  9. Dixit RP, Puthli SP (2009) Oral strip technology: overview and future potential. J Control Rel 139:94–107CrossRefGoogle Scholar
  10. El-Setouhy DA, Abd El-Malak NS (2010) Formulation of a novel tianeptine sodium orodispersible film. AAPS PharmSciTech 11(3):1018–1025CrossRefPubMedCentralPubMedGoogle Scholar
  11. Ghosh TK, Pfister WR (2005) Drug delivery to oral cavity: molecules to market. CRC Press, Taylor & Francis Group, FloridaCrossRefGoogle Scholar
  12. Haware RV, Chaudhari PD, Parakh SR, Bauer-Brandl A (2008) Development of a melting tablet containing promethazine HCl against motion sickness. AAPS PharmSciTech 9(3):1006–1015CrossRefPubMedCentralPubMedGoogle Scholar
  13. Kulkarni AS, Deokule HA, Mane MS, Ghadge DM (2010) Exploration of different polymers for use in the formulation of oral fast dissolving strips. J Curr Pharm Res 2(1):33–35Google Scholar
  14. Mahesh A, Shastri N, Sadanandam M (2010) Development of taste masked fast disintegrating films of levocetirizine dihydrochloride for oral use. Curr Drug Deliv 7(1):21–27CrossRefPubMedGoogle Scholar
  15. Mishra R, Amin A (2009) Formulation development of taste masked rapidly dissolving films of cetirizine hydrochloride. Pharm Tech USA 33:48–56Google Scholar
  16. Mishra R, Amin A (2011) Formulation and characterization of rapidly dissolving films of cetirizine hydrochloride using pullulan as a film forming agent. Indian J Pharm Edu Res 45:71–77Google Scholar
  17. Narang NA, Sharma JH (2011) Sublingual mucosa as a route for systemic drug delivery. Int J Pharm Pharm Sci 3(2):18–22Google Scholar
  18. Patel VF, Liu F, Brown MB (2011) Advances in oral transmucosal drug delivery. J Control Rel 153(2):106–116CrossRefGoogle Scholar
  19. Rajeswari C, Alka A, Javed A, Khar RK (2005) Cyclodextrins in drug delivery: an updated review. AAPS PharmSciTech 6(2):E329–E357CrossRefGoogle Scholar
  20. Rathbone MJ (1991) Human buccal absorption. A method for estimating the transfer kinetics of drugs across the human buccal membrane. Int J Pharm 69:103–108CrossRefGoogle Scholar

Copyright information

© The Korean Society of Pharmaceutical Sciences and Technology 2014

Authors and Affiliations

  • Jigar N. Shah
    • 1
    Email author
  • Kashyap N. Shah
    • 1
  • Tejal A. Mehta
    • 1
  1. 1.Department of Pharmaceutics & Pharmaceutical Technology, Institute of PharmacyNirma UniversityAhmedabadIndia

Personalised recommendations