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Amorphous solid dispersion of ledipasvir and sofosbuvir for enhancement of oral bioavailability

Yıl 2023, Cilt: 27 Sayı: 5, 1768 - 1776, 28.06.2025

Uday Kumar Thummala Eswar Gupta Maddi Prameela Rani Avula

Öz

The major goal of this research work was to augment bioavailability of the fixed-dose combination drugs, ledipasvir (LDV) and sofosbuvir (SBV) by developing orodispersible tablets and films and to estimate it by in vivo pharmacokinetic studies in rats. The pre-optimized amorphous solid dispersions of the LDV-SBV combination with HPMC E15 were made into orodispersible films (ODFs) and the pre-optimized inclusion complexes with dimethyl-β-cyclodextrin were made into orodispersible tablets (ODTs). The ODFs and ODTs were studied for the in vitro physical characterization studies and dissolution. Best of both the products were evaluated for in vivo pharmacokinetic studies in comparison with the marketed formulation of film coated tablets, Ledifos. The dissolution rate constants for the LDV from the optimized ODFs, ODTs and the marketed tablets were found to be 0.269, 0.13 and 0.073 min.-1 respectively. The dissolution rate constants for the SBV from the optimized ODFs, ODTs and the marketed tablets were found to be 0.302, 0.168 and 0.094 min.-1 respectively. Area under the curve (AUC) values for the LDV from the films, tablets and the marketed tablets were found to be 4231.4, 4050.3 and 3662.5 h*ng/mL respectively. AUC values for the SBV from the films, tablets and the marketed tablets were found to be 2173.2, 2084.6 and 1452.4 h*ng/mL respectively. Conclusion: The obtained results indicated that the optimized ODFs and the ODTs exhibited improved in vitro dissolution and in vivo bioavailability for the fixed-dose combination of LDV and SBV over the reference product.

Anahtar Kelimeler

Bioavailability ledipasvir sofosbuvir orodispersible tablets orodispersible films

Kaynakça

  • [1] Afdhal N, Zeuzem S, Kwo P, Chojkier M, Gitlin N, Puoti M, Romero-Gomez M, Zarski JP, Agarwal K, Buggisch P, Foster GR. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014; 370(20): 1889–1898. https://doi.org/10.1056/nejmoa1402454
  • [2] Rezaee-Zavareh MS, Hesamizadeh K, Behnava B, Alavian SM, Gholami-Fesharaki M, Sharafi H. Combination of ledipasvir and sofosbuvir for treatment of hepatitis C virus genotype 1 infection: systematic review and meta-analysis. Ann Hepatol. 2017; 16(2): 188–197. https://doi.org/10.5604/16652681.1231562
  • [3] German P, Mathias A, Brainard D, Kearney BP. Clinical pharmacokinetics and pharmacodynamics of ledipasvir/sofosbuvir, a fixed-dose combination tablet for the treatment of hepatitis C. Clin Pharmacokinet. 2016; 55(11): 1337–1351. https://doi.org/10.1007/s40262-016-0397-0
  • [4] Manogna K, Nagaveni P, Thyagaraju K. Enhancement of solubility of poorly soluble drugs by solid dispersion: An overview. Indian J Pharm Biol Res. 2017; 5(04): 17–23. https://doi.org/10.30750/ijpbr.5.4.4
  • [5] Savjani KT, Gajjar AK, Savjani JK. Drug solubility: importance and enhancement techniques. ISRN Pharm. 2012; 2012: 195727. https://doi.org/10.5402%2F2012%2F195727
  • [6] Khan AD, Singh L. Various techniques of bioavailability enhancement: a review. J Drug Deliv Ther. 2016; 6(3): 34–41. https://doi.org/10.22270/jddt.v6i3.1228
  • [7] Szabó E, Záhonyi P, Brecska D, Galata DL, Mészáros LA, Madarász L, Csorba K, Vass P, Hirsch E, Szafraniec-Szczęsny J, Csontos I. Comparison of amorphous solid dispersions of spironolactone prepared by spray drying and electrospinning: The influence of the preparation method on the dissolution properties. Mol Pharm. 2020; 18(1): 317–327. https://doi.org/10.1021/acs.molpharmaceut.0c00965
  • [8] Sid D, Baitiche M, Elbahri Z, Djerboua F, Boutahala M, Bouaziz Z, Le Borgne M. Solubility enhancement of mefenamic acid by inclusion complex with β-cyclodextrin: in silico modelling, formulation, characterisation, and in vitro studies. J Enzyme Inh Med Chem. 2021; 36(1): 605–617. https://doi.org/10.1080/14756366.2020.1869225
  • [9] Slavkova M, Breitkreutz J. Orodispersible drug formulations for children and elderly. Eur J Pharm Sci. 2015; 75: 2–9. https://doi.org/10.1016/j.ejps.2015.02.015
  • [10] Tawfik EA, Scarpa M, Abdelhakim HE, Bukhary HA, Craig DQ, Barker SA, Orlu M. A potential alternative orodispersible formulation to prednisolone sodium phosphate orally disintegrating tablets. Pharmaceutics. 2021; 13(1): 120. https://doi.org/10.3390/pharmaceutics13010120
  • [11] Srikar G, Gouthamib KS, Manasac B, Sirishad AS. Formulation optimization and characterization of amlodipine oral disintegrating tablets prepared by co-grinding technique. Der Pharm Lett. 2013; 5(4): 335–343.
  • [12] Guntaka PC, Lankalapalli S. A comparative study of ledipasvir solid dispersion technique using spray drying and hot-melt extrusion. Int J Pharm Sci Res. 2018; 9(12): 5145–5154. http://dx.doi.org/10.13040/IJPSR.0975-8232.9(12).5145-54
  • [13] Tekade AR, Yadav JN. A review on solid dispersion and carriers used therein for solubility enhancement of poorly water soluble drugs. Adv Pharm Bull. 2020; 10(3): 359. https://doi.org/10.34172%2Fapb.2020.044
  • [14] Vinay CH, Ahmed MG. Formulation and evaluation of mucoadhesive buccal tablets of candesartan. J Drug Deliv Ther. 2015; 5(5): 56–63. https://doi.org/10.22270/jddt.v5i5.1135
  • [15] Lee Y, Kim K, Kim M, Choi DH, Jeong SH. Orally disintegrating films focusing on formulation, manufacturing process, and characterization. J Pharm Investig. 2017; 47(3): 183–201. http://dx.doi.org/10.1007/s40005-017-0311-2
  • [16] Bansal S, Garg G. Design and optimization of fast dissolving film of losartan. Res J Pharm Technol. 2014; 7(11): 1211–1218.
  • [17] Nirmala D, Nandhini S, Sudhakar M. Design and evaluation of fast dissolving oral films of Zolpidem by solvent casting method. Asian J Pharm Res. 2016; 6(2): 67–71. http://dx.doi.org/10.5958/2231-5691.2016.00012.5
  • [18] Pitt KG, Heasley MG. Determination of the tensile strength of elongated tablets. Powder Technol. 2013; 238: 169–175. https://doi.org/10.1016/j.powtec.2011.12.060
  • [19] Malik K, Arora G, Singh I, Arora S. Lallemantia reylenne seeds as superdisintegrant: Formulation and evaluation of nimesulide orodispersible tablets. Int J Pharm Investig. 2011; 1(3): 192. https://doi.org/10.4103%2F2230-973X.85973
  • [20] Farid NF, Abdelwahab NS. Chromatographic analysis of ledipasvir and sofosbuvir: New treatment for chronic hepatitis C infection with application to human plasma. J Liq Chromatogr Relat Technol. 2017; 40(7): 327–332. http://dx.doi.org/10.1080/10826076.2017.1298526
  • [21] Kasawar GB, Farooqui M. Development and validation of a stability indicating RP-HPLC method for the simultaneous determination of related substances of albuterol sulfate and ipratropium bromide in nasal solution. J Pharm Biomed Anal. 2010; 52(1): 19–29. https://doi.org/10.1016/j.jpba.2009.11.026
  • [22] Lee G, Goosens KA. Sampling blood from the lateral tail vein of the rat. JoVE. 2015; 99: e52766. https://doi.org/10.3791%2F52766
  • [23] Zhang Y, Huo M, Zhou J, Xie S. PKSolver: An add-in program for pharmacokinetic and pharmacodynamic data analysis in Microsoft Excel. Comput Methods Programs Biomed. 2010; 99(3): 306–314. https://doi.org/10.1016/j.cmpb.2010.01.007
  • [24] Sanyang ML, Sapuan SM, Jawaid M, Ishak MR, Sahari J. Effect of plasticizer type and concentration on physical properties of biodegradable films based on sugar palm (Arenga pinnata) starch for food packaging. J Food Sci Technol. 2016; 53(1): 326–336. https://doi.org/10.1007/s13197-015-2009-7
  • [25] Young PM, Edge S, Staniforth JN, Steele DF, Price R. Dynamic vapor sorption properties of sodium starch glycolate disintegrants. Pharm Develop Technol. 2005; 10(2): 249–259. https://doi.org/10.1081/pdt-54448
  • [26] Zhao N, Augsburger LL. The influence of swelling capacity of superdisintegrants in different pH media on the dissolution of hydrochlorothiazide from directly compressed tablets. AAPS Pharmscitech. 2005; 6(1): E120–126. https://doi.org/10.1208%2Fpt060119
  • [27] Ferreira-Barbosa I, Araújo-Pierote JJ, Rodrigues de Menezes L, Trazzi-Prieto L, Frazão-Câmara JV, Sgarbosa de Araújo-Matuda L, Marchi GM, Maffei Sartini-Paulillo LA, Pimenta de Araujo CT. Effect of alternative solvent evaporation techniques on mechanical properties of primer-adhesive mixtures. Acta Odontol Latinoam. 2020; 33(2): 135–142.
  • [28] Khar RK. Lachman/Lieberman’s The Theory and Practice of Industrial Pharmacy. CBS Publishers & Distributors Pvt Ltd, India. 2013.
  • [29] Schönfeld BV, Westedt U, Wagner KG. Compression of amorphous solid dispersions prepared by hot-melt extrusion, spray drying and vacuum drum drying. Int J Pharm. 2021; 3: 100102. https://doi.org/10.1016/j.ijpx.2021.100102
  • [30] Yassin S, Goodwin DJ, Anderson A, Sibik J, Wilson DI, Gladden LF, Zeitler JA. The disintegration process in microcrystalline cellulose based tablets, part 1: influence of temperature, porosity and superdisintegrants. J Pharm Sci. 2015; 104(10): 3440–3450. https://doi.org/10.1002/jps.24544
  • [31] Srikar G, Kavitha G, Sirisha AS. Study of influence of povidone and sodium lauryl sulphate on performance of mouth dissolving tablets of mirtazapine. Sch Acad J Pharm. 2014; 3(2): 201–207.
  • [32] Lv Y, Luo BY, LaBadie RR, Zhu H, Feng Y, Ernst C, Crownover PH, Liang Y, Zhao Q. Bioequivalence and bioavailability of an orodispersible tablet of sildenafil citrate in healthy Chinese male subjects. Clin Pharmacol Drug Develop. 2020; 9(5): 573–581. https://doi.org/10.1002/cpdd.806
  • [33] Kannuri R, Challa T, Chamarthi H. Taste masking and evaluation methods for orodispersible tablets. Int J Pharm Ind Res. 2011; 1(3): 201–210. https://doi.org/10.1016/j.ijpharm.2021.120725
  • [34] Tawfik EA, Scarpa M, Abdelhakim HE, Bukhary HA, Craig DQ, Barker SA, Orlu M. A potential alternative orodispersible formulation to prednisolone sodium phosphate orally disintegrating tablets. Pharmaceutics. 2021; 13(1): 120. https://doi.org/10.3390/pharmaceutics13010120
  • [35] Brniak W, Maślak E, Jachowicz R. Orodispersible films and tablets with prednisolone microparticles. Eur J Pharm Sci. 2015; 75: 81–90. https://doi.org/10.1016/j.ejps.2015.04.006
  • [36] Aderibigbe BA, Buyana B. Alginate in wound dressings. Pharmaceutics. 2018; 10(2): 42. https://doi.org/10.3390/pharmaceutics10020042
  • [37] Teng R, Hammarberg M, Carlson GF, Bokelund-Singh S, Ruderfelt T, Blychert E. Pharmacokinetic profiles of ticagrelor orodispersible tablets in healthy Western and Japanese subjects. Clin Drug Investig. 2017; 37(11): 1035–1045. https://doi.org/10.1007/s40261-017-0554-8

Yıl 2023, Cilt: 27 Sayı: 5, 1768 - 1776, 28.06.2025

Uday Kumar Thummala Eswar Gupta Maddi Prameela Rani Avula

Öz

Kaynakça

  • [1] Afdhal N, Zeuzem S, Kwo P, Chojkier M, Gitlin N, Puoti M, Romero-Gomez M, Zarski JP, Agarwal K, Buggisch P, Foster GR. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014; 370(20): 1889–1898. https://doi.org/10.1056/nejmoa1402454
  • [2] Rezaee-Zavareh MS, Hesamizadeh K, Behnava B, Alavian SM, Gholami-Fesharaki M, Sharafi H. Combination of ledipasvir and sofosbuvir for treatment of hepatitis C virus genotype 1 infection: systematic review and meta-analysis. Ann Hepatol. 2017; 16(2): 188–197. https://doi.org/10.5604/16652681.1231562
  • [3] German P, Mathias A, Brainard D, Kearney BP. Clinical pharmacokinetics and pharmacodynamics of ledipasvir/sofosbuvir, a fixed-dose combination tablet for the treatment of hepatitis C. Clin Pharmacokinet. 2016; 55(11): 1337–1351. https://doi.org/10.1007/s40262-016-0397-0
  • [4] Manogna K, Nagaveni P, Thyagaraju K. Enhancement of solubility of poorly soluble drugs by solid dispersion: An overview. Indian J Pharm Biol Res. 2017; 5(04): 17–23. https://doi.org/10.30750/ijpbr.5.4.4
  • [5] Savjani KT, Gajjar AK, Savjani JK. Drug solubility: importance and enhancement techniques. ISRN Pharm. 2012; 2012: 195727. https://doi.org/10.5402%2F2012%2F195727
  • [6] Khan AD, Singh L. Various techniques of bioavailability enhancement: a review. J Drug Deliv Ther. 2016; 6(3): 34–41. https://doi.org/10.22270/jddt.v6i3.1228
  • [7] Szabó E, Záhonyi P, Brecska D, Galata DL, Mészáros LA, Madarász L, Csorba K, Vass P, Hirsch E, Szafraniec-Szczęsny J, Csontos I. Comparison of amorphous solid dispersions of spironolactone prepared by spray drying and electrospinning: The influence of the preparation method on the dissolution properties. Mol Pharm. 2020; 18(1): 317–327. https://doi.org/10.1021/acs.molpharmaceut.0c00965
  • [8] Sid D, Baitiche M, Elbahri Z, Djerboua F, Boutahala M, Bouaziz Z, Le Borgne M. Solubility enhancement of mefenamic acid by inclusion complex with β-cyclodextrin: in silico modelling, formulation, characterisation, and in vitro studies. J Enzyme Inh Med Chem. 2021; 36(1): 605–617. https://doi.org/10.1080/14756366.2020.1869225
  • [9] Slavkova M, Breitkreutz J. Orodispersible drug formulations for children and elderly. Eur J Pharm Sci. 2015; 75: 2–9. https://doi.org/10.1016/j.ejps.2015.02.015
  • [10] Tawfik EA, Scarpa M, Abdelhakim HE, Bukhary HA, Craig DQ, Barker SA, Orlu M. A potential alternative orodispersible formulation to prednisolone sodium phosphate orally disintegrating tablets. Pharmaceutics. 2021; 13(1): 120. https://doi.org/10.3390/pharmaceutics13010120
  • [11] Srikar G, Gouthamib KS, Manasac B, Sirishad AS. Formulation optimization and characterization of amlodipine oral disintegrating tablets prepared by co-grinding technique. Der Pharm Lett. 2013; 5(4): 335–343.
  • [12] Guntaka PC, Lankalapalli S. A comparative study of ledipasvir solid dispersion technique using spray drying and hot-melt extrusion. Int J Pharm Sci Res. 2018; 9(12): 5145–5154. http://dx.doi.org/10.13040/IJPSR.0975-8232.9(12).5145-54
  • [13] Tekade AR, Yadav JN. A review on solid dispersion and carriers used therein for solubility enhancement of poorly water soluble drugs. Adv Pharm Bull. 2020; 10(3): 359. https://doi.org/10.34172%2Fapb.2020.044
  • [14] Vinay CH, Ahmed MG. Formulation and evaluation of mucoadhesive buccal tablets of candesartan. J Drug Deliv Ther. 2015; 5(5): 56–63. https://doi.org/10.22270/jddt.v5i5.1135
  • [15] Lee Y, Kim K, Kim M, Choi DH, Jeong SH. Orally disintegrating films focusing on formulation, manufacturing process, and characterization. J Pharm Investig. 2017; 47(3): 183–201. http://dx.doi.org/10.1007/s40005-017-0311-2
  • [16] Bansal S, Garg G. Design and optimization of fast dissolving film of losartan. Res J Pharm Technol. 2014; 7(11): 1211–1218.
  • [17] Nirmala D, Nandhini S, Sudhakar M. Design and evaluation of fast dissolving oral films of Zolpidem by solvent casting method. Asian J Pharm Res. 2016; 6(2): 67–71. http://dx.doi.org/10.5958/2231-5691.2016.00012.5
  • [18] Pitt KG, Heasley MG. Determination of the tensile strength of elongated tablets. Powder Technol. 2013; 238: 169–175. https://doi.org/10.1016/j.powtec.2011.12.060
  • [19] Malik K, Arora G, Singh I, Arora S. Lallemantia reylenne seeds as superdisintegrant: Formulation and evaluation of nimesulide orodispersible tablets. Int J Pharm Investig. 2011; 1(3): 192. https://doi.org/10.4103%2F2230-973X.85973
  • [20] Farid NF, Abdelwahab NS. Chromatographic analysis of ledipasvir and sofosbuvir: New treatment for chronic hepatitis C infection with application to human plasma. J Liq Chromatogr Relat Technol. 2017; 40(7): 327–332. http://dx.doi.org/10.1080/10826076.2017.1298526
  • [21] Kasawar GB, Farooqui M. Development and validation of a stability indicating RP-HPLC method for the simultaneous determination of related substances of albuterol sulfate and ipratropium bromide in nasal solution. J Pharm Biomed Anal. 2010; 52(1): 19–29. https://doi.org/10.1016/j.jpba.2009.11.026
  • [22] Lee G, Goosens KA. Sampling blood from the lateral tail vein of the rat. JoVE. 2015; 99: e52766. https://doi.org/10.3791%2F52766
  • [23] Zhang Y, Huo M, Zhou J, Xie S. PKSolver: An add-in program for pharmacokinetic and pharmacodynamic data analysis in Microsoft Excel. Comput Methods Programs Biomed. 2010; 99(3): 306–314. https://doi.org/10.1016/j.cmpb.2010.01.007
  • [24] Sanyang ML, Sapuan SM, Jawaid M, Ishak MR, Sahari J. Effect of plasticizer type and concentration on physical properties of biodegradable films based on sugar palm (Arenga pinnata) starch for food packaging. J Food Sci Technol. 2016; 53(1): 326–336. https://doi.org/10.1007/s13197-015-2009-7
  • [25] Young PM, Edge S, Staniforth JN, Steele DF, Price R. Dynamic vapor sorption properties of sodium starch glycolate disintegrants. Pharm Develop Technol. 2005; 10(2): 249–259. https://doi.org/10.1081/pdt-54448
  • [26] Zhao N, Augsburger LL. The influence of swelling capacity of superdisintegrants in different pH media on the dissolution of hydrochlorothiazide from directly compressed tablets. AAPS Pharmscitech. 2005; 6(1): E120–126. https://doi.org/10.1208%2Fpt060119
  • [27] Ferreira-Barbosa I, Araújo-Pierote JJ, Rodrigues de Menezes L, Trazzi-Prieto L, Frazão-Câmara JV, Sgarbosa de Araújo-Matuda L, Marchi GM, Maffei Sartini-Paulillo LA, Pimenta de Araujo CT. Effect of alternative solvent evaporation techniques on mechanical properties of primer-adhesive mixtures. Acta Odontol Latinoam. 2020; 33(2): 135–142.
  • [28] Khar RK. Lachman/Lieberman’s The Theory and Practice of Industrial Pharmacy. CBS Publishers & Distributors Pvt Ltd, India. 2013.
  • [29] Schönfeld BV, Westedt U, Wagner KG. Compression of amorphous solid dispersions prepared by hot-melt extrusion, spray drying and vacuum drum drying. Int J Pharm. 2021; 3: 100102. https://doi.org/10.1016/j.ijpx.2021.100102
  • [30] Yassin S, Goodwin DJ, Anderson A, Sibik J, Wilson DI, Gladden LF, Zeitler JA. The disintegration process in microcrystalline cellulose based tablets, part 1: influence of temperature, porosity and superdisintegrants. J Pharm Sci. 2015; 104(10): 3440–3450. https://doi.org/10.1002/jps.24544
  • [31] Srikar G, Kavitha G, Sirisha AS. Study of influence of povidone and sodium lauryl sulphate on performance of mouth dissolving tablets of mirtazapine. Sch Acad J Pharm. 2014; 3(2): 201–207.
  • [32] Lv Y, Luo BY, LaBadie RR, Zhu H, Feng Y, Ernst C, Crownover PH, Liang Y, Zhao Q. Bioequivalence and bioavailability of an orodispersible tablet of sildenafil citrate in healthy Chinese male subjects. Clin Pharmacol Drug Develop. 2020; 9(5): 573–581. https://doi.org/10.1002/cpdd.806
  • [33] Kannuri R, Challa T, Chamarthi H. Taste masking and evaluation methods for orodispersible tablets. Int J Pharm Ind Res. 2011; 1(3): 201–210. https://doi.org/10.1016/j.ijpharm.2021.120725
  • [34] Tawfik EA, Scarpa M, Abdelhakim HE, Bukhary HA, Craig DQ, Barker SA, Orlu M. A potential alternative orodispersible formulation to prednisolone sodium phosphate orally disintegrating tablets. Pharmaceutics. 2021; 13(1): 120. https://doi.org/10.3390/pharmaceutics13010120
  • [35] Brniak W, Maślak E, Jachowicz R. Orodispersible films and tablets with prednisolone microparticles. Eur J Pharm Sci. 2015; 75: 81–90. https://doi.org/10.1016/j.ejps.2015.04.006
  • [36] Aderibigbe BA, Buyana B. Alginate in wound dressings. Pharmaceutics. 2018; 10(2): 42. https://doi.org/10.3390/pharmaceutics10020042
  • [37] Teng R, Hammarberg M, Carlson GF, Bokelund-Singh S, Ruderfelt T, Blychert E. Pharmacokinetic profiles of ticagrelor orodispersible tablets in healthy Western and Japanese subjects. Clin Drug Investig. 2017; 37(11): 1035–1045. https://doi.org/10.1007/s40261-017-0554-8
Toplam 37 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Eczacılık ve İlaç Bilimleri (Diğer)
Bölüm Articles
Yazarlar

Uday Kumar Thummala 0009-0000-8221-9679

Eswar Gupta Maddi 0000-0001-7712-2303

Prameela Rani Avula 0000-0002-1681-8021

Yayımlanma Tarihi 28 Haziran 2025
Yayımlandığı Sayı Yıl 2023 Cilt: 27 Sayı: 5

Kaynak Göster

APA Thummala, U. K., Maddi, E. G., & Avula, P. R. (2025). Amorphous solid dispersion of ledipasvir and sofosbuvir for enhancement of oral bioavailability. Journal of Research in Pharmacy, 27(5), 1768-1776.
AMA Thummala UK, Maddi EG, Avula PR. Amorphous solid dispersion of ledipasvir and sofosbuvir for enhancement of oral bioavailability. J. Res. Pharm. Temmuz 2025;27(5):1768-1776.
Chicago Thummala, Uday Kumar, Eswar Gupta Maddi, ve Prameela Rani Avula. “Amorphous Solid Dispersion of Ledipasvir and Sofosbuvir for Enhancement of Oral Bioavailability”. Journal of Research in Pharmacy 27, sy. 5 (Temmuz 2025): 1768-76.
EndNote Thummala UK, Maddi EG, Avula PR (01 Temmuz 2025) Amorphous solid dispersion of ledipasvir and sofosbuvir for enhancement of oral bioavailability. Journal of Research in Pharmacy 27 5 1768–1776.
IEEE U. K. Thummala, E. G. Maddi, ve P. R. Avula, “Amorphous solid dispersion of ledipasvir and sofosbuvir for enhancement of oral bioavailability”, J. Res. Pharm., c. 27, sy. 5, ss. 1768–1776, 2025.
ISNAD Thummala, Uday Kumar vd. “Amorphous Solid Dispersion of Ledipasvir and Sofosbuvir for Enhancement of Oral Bioavailability”. Journal of Research in Pharmacy 27/5 (Temmuz 2025), 1768-1776.
JAMA Thummala UK, Maddi EG, Avula PR. Amorphous solid dispersion of ledipasvir and sofosbuvir for enhancement of oral bioavailability. J. Res. Pharm. 2025;27:1768–1776.
MLA Thummala, Uday Kumar vd. “Amorphous Solid Dispersion of Ledipasvir and Sofosbuvir for Enhancement of Oral Bioavailability”. Journal of Research in Pharmacy, c. 27, sy. 5, 2025, ss. 1768-76.
Vancouver Thummala UK, Maddi EG, Avula PR. Amorphous solid dispersion of ledipasvir and sofosbuvir for enhancement of oral bioavailability. J. Res. Pharm. 2025;27(5):1768-76.