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Influence of Formulation Factors on Tablet Formulations with Liquid Permeation Enhancer Using Factorial Design

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Abstract

For a drug with low bioavailability, a matrix tablet with liquid permeation enhancer (Labrasol®) was formulated. Factorial design was used to evaluate the effect of three formulation factors: drug percentage, polymer type (Methocel® K100M or Eudragit® L 100-55), and tablet binder percentage (Plasdone® S-630) on tablet characteristics. Tablets were prepared by direct compression and characterized. Compressibility index values ranged between 15.90% and 29.87% and tablet hardness values from 7.8 to 29.78 Kp. Eudragit®-containing formulations had better compressibility index values with higher tablet hardness. Time for 75% of drug release (T 75) was calculated, and formulations containing Eudragit® L 100-55 had faster release rates than tablet formulations with Methocel® K100M. Formulations with Methocel® K100M fit well in the Higuchi model as indicated by their R 2 values (>0.98). Among all the formulation factors studied, polymer type displayed the highest and statistically significant effect on compressibility index, tablet hardness, and dissolution rate. Statistical design helped in better understanding the effect of formulation factors on tablet characteristics important for designing formulations with desired characteristics.

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References

  1. Aungst BJ. Novel formulation strategies for improving oral bioavailability of drugs with poor membrane permeation or presystemic metabolism. J Pharm Sci. 1993;82(10):979–87.

    Article  CAS  PubMed  Google Scholar 

  2. Irwin GM, Kostenbauder HB, Dittert LW, Staples R, Misher A, Swintosky JV. Enhancement of gastrointestinal absorption of a quaternary ammonium compound by trichloroacetate. J Pharm Sci. 1969;58(3):313–5.

    Article  CAS  PubMed  Google Scholar 

  3. Caramazza I, D'Atri G, Bossi ML, De Ponti F, D'Angelo L, Crema A. Intraduodenal absorption of the new UF-heparin salt ITF 1057 in the conscious dog. Thromb Res. 1991;62(6):785–9.

    Article  CAS  PubMed  Google Scholar 

  4. Levy G, Reuning RH. Effect of complex formation on drug absorption. I. Complexes of salicylic acid with absorbable and nonabsorbable compounds. J Pharm Sci. 1964;53:1471–5.

    Article  CAS  PubMed  Google Scholar 

  5. Uekama K, Narisawa S, Hirayama F, Otagiri M. Improvement of dissolution and absorption characteristics of benzodiazepines by cyclodextrin complexation. Int J Pharm. 1983;16(3):327–38.

    Article  CAS  Google Scholar 

  6. Sharma P, Varma MV, Chawla HP, Panchagnula R. Absorption enhancement, mechanistic and toxicity studies of medium chain fatty acids, cyclodextrins and bile salts as peroral absorption enhancers. Farmaco. 2005;60(11-12):884–93.

    Article  CAS  PubMed  Google Scholar 

  7. Pouton CW. Lipid formulations for oral administration of drugs: non-emulsifying, self-emulsifying and “self-microemulsifying” drug delivery systems. Eur J Pharm Sci. 2000;11(Suppl 2):S93–8.

    Article  CAS  PubMed  Google Scholar 

  8. Nazzal S, Nutan M, Palamakula A, Shah R, Zaghloul AA, Khan MA. Optimization of a self-nanoemulsified tablet dosage form of Ubiquinone using response surface methodology: effect of formulation ingredients. Int J Pharm. 2002;240(1–2):103–14.

    Article  CAS  PubMed  Google Scholar 

  9. Amidon GL, Lennernas H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res. 1995;12(3):413–20.

    Article  CAS  PubMed  Google Scholar 

  10. Yuksel N, Karatas A, Ozkan Y, Savaser A, Ozkan SA, Baykara T. Enhanced bioavailability of piroxicam using Gelucire 44/14 and Labrasol: in vitro and in vivo evaluation. Eur J Pharm Biopharm. 2003;56(3):453–9.

    Article  CAS  PubMed  Google Scholar 

  11. Rama Prasad YV, Eaimtrakarn S, Ishida M, Kusawake Y, Tawa R, Yoshikawa Y, et al. Evaluation of oral formulations of gentamicin containing Labrasol in beagle dogs. Int J Pharm. 2003;268(1-2):13–21.

    Article  CAS  PubMed  Google Scholar 

  12. Djordjevic L, Primorac M, Stupar M, Krajisnik D. Characterization of caprylocaproyl macrogolglycerides based microemulsion drug delivery vehicles for an amphiphilic drug. Int J Pharm. 2004;271(1–2):11–9.

    Article  CAS  PubMed  Google Scholar 

  13. Koga K, Kusawake Y, Ito Y, Sugioka N, Shibata N, Takada K. Enhancing mechanism of Labrasol on intestinal membrane permeability of the hydrophilic drug gentamicin sulfate. Eur J Pharm Biopharm. 2006;64(1):82–91.

    Article  CAS  PubMed  Google Scholar 

  14. Ito Y, Arai H, Uchino K, Iwasaki K, Shibata N, Takada K. Effect of adsorbents on the absorption of lansoprazole with surfactant. Int J Pharm. 2005;289(1–2):69–77.

    Article  CAS  PubMed  Google Scholar 

  15. Ito Y, Kusawake T, Ishida M, Tawa R, Shibata N, Takada K. Oral solid gentamicin preparation using emulsifier and adsorbent. J Control Release. 2005;105(1–2):23–31.

    Article  CAS  PubMed  Google Scholar 

  16. Ito Y, Kusawake T, Prasad YV, Sugioka N, Shibata N, Takada K. Preparation and evaluation of oral solid heparin using emulsifier and adsorbent for in vitro and in vivo studies. Int J Pharm. 2006;317(2):114–9.

    Article  CAS  PubMed  Google Scholar 

  17. Cabot-Corporation. Untreated fumed silica: Cab-O-Sil EH5. Cabot Corporation 2006.

  18. Takka S, Singh Bharaj S, Sakr A. Influence of methacrylic acid and hydroxypropylmethyl cellulose on the tablet properties and in vitro release of dextromethorphan hydrobromide. Die Pharmazie. 2003;58(12):886–90.

    CAS  PubMed  Google Scholar 

  19. Nellore RV, Rekhi GS, Hussain AS, Tillman LG, Augsburger LL. Development of metoprolol tartrate extended-release matrix tablet formulations for regulatory policy consideration. J Control Release. 1998;50(1–3):247–56.

    Article  CAS  PubMed  Google Scholar 

  20. Solinis MA, de la Cruz Y, Hernandez RM, Gascon AR, Calvo B, Pedraz JL. Release of ketoprofen enantiomers from HPMC K100M matrices—diffusion studies. Int J Pharm. 2002;239(1–2):61–8.

    Article  CAS  PubMed  Google Scholar 

  21. Gambhire MN, Ambade KW, Kurmi SD, Kadam VJ, Jadhav KR. Development and in vitro evaluation of an oral floating matrix tablet formulation of diltiazem hydrochloride. AAPS PharmSciTech. 2007;8(3):E73.

    Article  PubMed  Google Scholar 

  22. Takka S, Rajbhandari S, Sakr A. Effect of anionic polymers on the release of propranolol hydrochloride from matrix tablets. Eur J Pharm Biopharm. 2001;52(1):75–82.

    Article  CAS  PubMed  Google Scholar 

  23. Moroni A. A Novel Copovidone Binder for Dry Granulation and Direct-Compression Tableting. Pharm Technol. 2001;25(9):8–12.

    Google Scholar 

  24. Gao JZ, Jain A, Motheram R, Gray DB, Hussain MA. Fluid bed granulation of a poorly water soluble, low density, micronized drug: comparison with high shear granulation. Int J Pharm. 2002;237(1–2):1–14.

    Article  CAS  PubMed  Google Scholar 

  25. Khanvilkar KH, Huang Y, Moore AD. Influence of hydroxypropyl methylcellulose mixture, apparent viscosity, and tablet hardness on drug release using a 2(3) full factorial design. Drug Dev Ind Pharm. 2002;28(5):601–8.

    Article  CAS  PubMed  Google Scholar 

  26. Akin-Ajani OD, Itiola OA, Odeku OA. Effects of plantain and corn starches on the mechanical and disintegration properties of paracetamol tablets. AAPS PharmSciTech. 2005;6(3):E458–63.

    Article  PubMed  Google Scholar 

  27. Nazzal S, Khan MA. Controlled release of a self-emulsifying formulation from a tablet dosage form: stability assessment and optimization of some processing parameters. Int J Pharm. 2006;315(1–2):110–21.

    Article  CAS  PubMed  Google Scholar 

  28. Moore JW, Flanner HH. Mathematical comparison of dissolution profiles. Pharm Technol. 1996;20(6):64–75.

    Google Scholar 

  29. Narendra C, Srinath MS, Babu G. Optimization of bilayer floating tablet containing metoprolol tartrate as a model drug for gastric retention. AAPS PharmSciTech. 2006;7(2):E34.

    Article  CAS  PubMed  Google Scholar 

  30. Carr RL. Evaluating flow properties of solids. Chem Eng. 1965;72:163–8.

    CAS  Google Scholar 

  31. USP31-NF26. Chapter 1174 Powder flow. USP31–NF26 ed. Rockville, MD 2009:618.

  32. Schulze MD, Williams RO, McGinity JW. Compaction properties of acrylic resin polymers with plastic and brittle drugs. Drug Dev Ind Pharm. 1990;16(5):741–54.

    Article  CAS  Google Scholar 

  33. Tatavarti AS, Muller FX, Hoag SW. Evaluation of the deformation behavior of binary systems of methacrylic acid copolymers and hydroxypropyl methylcellulose using a compaction simulator. Int J Pharm. 2008;348(1–2):46–53.

    Article  CAS  PubMed  Google Scholar 

  34. Costa P, Sousa Lobo JM. Modeling and comparison of dissolution profiles. Eur J Pharm Sci. 2001;13(2):123–33.

    Article  CAS  PubMed  Google Scholar 

  35. Mehta KA, Kislalioglu MS, Phuapradit W, Malick AW, Shah NH. Release performance of a poorly soluble drug from a novel, Eudragit-based multi-unit erosion matrix. Int J Pharm. 2001;213(1–2):7–12.

    Article  CAS  PubMed  Google Scholar 

  36. Higuchi T. Physical chemical analysis of percutaneous absorption process from creams and ointments. J Soc Cosmet Chem. 1960;11:85–97.

    Google Scholar 

  37. Higuchi T. Rate of release of medicaments from ointment bases containing drugs in suspension. J Pharm Sci. 1961;50:874–5.

    Article  CAS  PubMed  Google Scholar 

  38. Higuchi T. Mechanism of sustained-action medication. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J Pharm Sci. 1963;52:1145–9.

    Article  CAS  PubMed  Google Scholar 

  39. Oren PL, Seidler WMK, inventors; Sustained release matrix patent 1990, 4,968,508.

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Acknowledgements

This project has been supported with funds from the U.S. National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN26620050047C. The authors wish to thank Ms. Manjula Prasad and Dr. Jane Han for the HPLC analysis of the dissolution samples.

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  1. Pharmaceutical Sciences, Biosciences Division, SRI International, 333 Ravenswood Avenue, Menlo Park, California, 94025, USA

    Naveen K. Bejugam, Helen J. Parish & Gita N. Shankar

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  1. Naveen K. Bejugam
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  2. Helen J. Parish
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  3. Gita N. Shankar
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Correspondence to Gita N. Shankar.

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Bejugam, N.K., Parish, H.J. & Shankar, G.N. Influence of Formulation Factors on Tablet Formulations with Liquid Permeation Enhancer Using Factorial Design. AAPS PharmSciTech 10, 1437–1443 (2009). https://doi.org/10.1208/s12249-009-9345-8

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