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Abstract
Background: Marketed tablets of drugs must fulfill the required standards of dissolution to guarantee the equivalent of reference. Atorvastatin calcium needs enhanced dissolution since this compound includes Biopharmaceutical Classification System (BCS) Class II drugs with low solubility and high permeability. This means that dissolution affects the bioavailability of drugs.
Objective: This research aimed to develop a formulation of atorvastatin calcium tablets by liquisolid system using propylene glycol as a solvent and some carrier materials that are equivalent to the reference product.
Method: Different formulations of liquisolid tablets were conducted using different quantities of carrier materials like Avicel PH 101, Avicel PH 102, and Neusilin US2, with Aerosil 200 as the coating material. The liquisolid powder was compressed into tablets by the direct compressing method. X-ray diffractometry (XRD) and FTIR analysis were used to find out more about the liquisolid tablets' properties and how the drug and excipients might interact with each other.
Results: The liquisolid tablets of atorvastatin calcium were within the acceptable limit criteria. The dissolution of AA4 tablets was higher compared to conventional and marketed tablets. The XRD and Fourier transform infrared (FTIR) analyses showed no chemical interactions between the drug and the excipient.
Conclusion: The liquisolid formulation can then be developed as an alternative for the production of atorvastatin calcium tablets in the pharmaceutical industry.
Keywords: Atorvastatin calcium, dissolution, liquisolid, propylene glycol
Intisari
Latar belakang: Sediaan tablet yang dipasarkan harus memenuhi standar disolusi yang ditetapkan untuk menjamin ekivalensinya dengan produk standar. Kalsium atorvastatin perlu ditingkatkan disolusinya, karena termasuk dalam kelas II Sistem Klasifikasi Biofarmasetik (BCS) dengan sifat kelarutan yang rendah dan permeabilitas yang tinggi. Disolusi kalsium atorvastatin mempengaruhi bioavailabilitasnya.
Tujuan: Penelitian ini bertujuan mengembangkan formulasi tablet likuisolid menggunakan pelarut propilen glikol dan beberapa bahan pembawa sebagai alternatif formulasi tablet kalsium atorvastatin yang bioekivalen dengan produk standar.
Metode: Tablet likuisolid dibuat dengan menambahkan berbagai komposisi bahan pembawa seperti Avicel PH 101, Avicel PH 102, dan Neusilin US2, serta Aerosil 200 sebagai pelapis pada dispersi kalsium atorvastatin dalam propilen glikol hingga terbentuk serbuk likuisolid. Serbuk likuisolid dikompresi langsung menjadi tablet setelah ditambahkan penghancur dan pelincir. Tablet likuisolid kalsium atorvastatin dievaluasi karakteristiknya dan dianalisis dengan XRD dan FTIR untuk mengetahui adanya interaksi antara zat aktif dengan eksipien yang digunakan.
Hasil: Tablet likuisolid kalsium atorvastatin memenuhi kriteria tablet dalam literatur dan kompendia. Tablet likuisolid AA4 memenuhi kriteria penerimaan uji disolusi dalam Farmakope Indonesia (FI). Hasil analisis XRD dan FTIR tablet likuisolid AA4 menunjukkan tidak ada interaksi kimia antara zat aktif dengan eksipien.
Kesimpulan: Formulasi tablet likuisolid dapat dikembangkan sebagai alternatif untuk produksi tablet kalsium atorvastatin di industri farmasi.
Kata kunci: Kalsium atorvastatin, disolusi, likuisolid, propilen glikol
Article Details
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References
- Baskaran M., Talluri K.B., Kuppusamy G., Karri V.V.S.R., & Kollipara R. (2016). Formulation Development of Atorvastatin Calcium Tablets by Gel Liquisolid Compact Technique for Improving Solid State Stability and Dissolution Profile. Journal of Drug Research and Development, 2(4), 1-7. https://dx.doi.org/10.16966/2470-1009.123
- Chouksey R., Kumar Jain A., Pandey H., & Maithil A. (2011). Development and Bioavailability Studies of Atorvastatin Nanoemulsion. International Journal of Pharmacy & Life Sciences, 2(8), 982–988.
- Gozali D., Putra A.F.C., & Sopyan I. (2014). Pengaruh Modifikasi Kristal Kalsium Atorvastatin Terhadap Laju Disolusi. Bionatura-Jurnal Ilmu-Ilmu Hayati dan Fisik, 16(2), 83–88.
- Gozali D., Wardhana Y.W., & Shofa. (2015). Formulasi dan Evaluasi Tablet Dispersi Padat Kalsium Atorvastatin. Pharmascience, 2(2), 63–70.
- Kadu P.J., Kushare S.S., Thacker D.D., & Gattani S.G. (2011). Enhancement of Oral Bioavailability of Atorvastatin Calcium by Self-Emulsifying Drug Delivery Systems (SEDDS). Pharmaceutical Development and Technology, 16(1), 65–74. https://doi.org/10.3109/10837450903499333
- Khan F.N., & Dehghan M.H.G. (2011). Enhanced Bioavailability of Atorvastatin Calcium from Stabilized Gastric Resident Formulation. AAPS PharmSciTech, 12(4), 1077–1086. https://doi.org/10.1208/s12249-011-9673-3
- Lu M., Xing H., Jiang J., Chen X., Yang T., Wang D., & Ding P. (2016). Liquisolid Technique and Its Applications in Pharmaceutics. Asian Journal of Pharmaceutical Sciences, 12(2), 115–123. https://doi.org/10.1016/j.ajps.2016.09.007
- Oishi T.S., Nimmi I., & Islam S.M.A. (2011). Comparative In Vitro Bioequivalence Analysis of Some Generic Tablets of Atorvastatin, a BCS Class II Compound. Bangladesh Pharmaceutical Journal, 14(1), 61–66.
- Panghal D., Nangpal M., Thakur G.S., & Arora S. (2014). Dissolution Improvement of Atorvastatin Calcium using Modified Locust Bean Gum by the Solid Dispersion Technique. Scientia Pharmaceutica, 82(1), 177–191. https://doi.org/10.3797/scipharm.1301-23
- Patil P.R., Mahaparale P.R., & Shaikh K.U. (2021). Formulation, Development and Evaluation of Atorvastatin Ethosomal Gel. International Journal of Pharmaceutical Sciences and Research, 12(3), 1849–1859. https://doi.org/10.13040/IJPSR.0975-8232.12(3).1849-59
- Popy F.A., Dewan I., Parvin M.N., & Islam S.M.A. (2012). Evaluation of In Vitro Equivalence for Tablets Containing the Poorly WaterSoluble Compound Atorvastatin. Dissolution Technologies, 19(4), 30–33.
- Prabhu P., & Patravale V. (2015). Dissolution Enhancement of Atorvastatin Calcium by Co-Grinding Technique. Drug Delivery Translational Research, 6(4), 380–391. https://doi.org/10.1007/s13346-015-0271-x
- Rodde M.S., Divase G.T., Devkar T.B., & Tekade A.R. (2014). Solubility and Bioavailability Enhancement of Poorly Aqueous Soluble Atorvastatin: In Vitro , Ex Vivo , and In Vivo Studies. Biomed Research International, 2014, 1–10. https://doi.org/10.1155/2014/463895
- Sanjeev R., Gubbi, & Jarag, R. (2010). Formulation and Characterization of Atorvastatin Calcium Liquisolid Compacts. Asian Journal Pharmaceutical Sciences, 5(2), 50–60.
- Snela A., Jadach B., Froelich A., Skotnicki M., Milczewska K., Rojewska M., Voelkel A., Prochaska K., & Lulek J. (2019). Self-Emulsifying Drug Delivery Systems with Atorvastatin Adsorbed on Solid Carriers: Formulation nd In Vitro Drug Release Studies. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 577, 281–290. https://doi.org/10.1016/j.colsurfa.2019.05.062
- Sonje V.M., Kumar L., Meena C.L., Kohli G., Puri V., Jain R., Bansal A.K., & Brittain H.G. (2010). Atorvastatin Calcium. Profiles of Drug Substances, Excipients and Related Methodology, 35, 1-70. https://doi.org/10.1016/S1871-5125(10)35001-1
- Spireas S. (1998). Liquisolid Systems and Methods of Preparing Same. Unites States Patent. 1–9.
- Vraníková B., & Gajdziok J. (2013). Liquisolid Systems and Aspects Influencing Their Research and Development. Acta Pharmaceutica, 63, 447–465. https://doi.org/10.2478/acph-2013-0034
- Vraníková B., Gajdziok J., & Vetchý D. (2015). Modern Evaluation of Liquisolid Systems with Varying Amounts of Liquid Phase Prepared Using Two Different Methods. Biomed Research International, 1–12. https://doi.org/10.1155/2015/608435
- Wicaksono Y., Setyawan D., Siswandono S., & Siswoyo T.A. (2019). Preparation and Characterization of a Novel Cocrystal of Atorvastatin Calcium with Succinic Acid Coformer. Indonesian Journal of Chemistry, 19(3), 660-667. https://doi.org/10.22146/ijc.35801
- Wicaksono Y., Wisudyaningsih B., & Siswoyo T.A. (2017). Enhancement of Solubility and Dissolution Rate of Atorvastatin Calcium by Co-Crystallization. Tropical Journal of Pharmaceutical Research, 16(7), 1497-1502. https://doi.org/10.4314/tjpr.v16i7.6
- Windriyati Y.N., Badriyah M., Kusumaningtyas D.A., & Riesmalia R.L. (2020). Liquisolid Tablets Formulation of Atorvastatin Calcium Using Polyethylene Glycol 400 as Solvent and Some Carrier Materials. Indonesian Journal of Pharmacy, 31(4), 305–311. https://doi.org/10.22146/ijp.1138
- Yadavb A.V., & Yardava V.B. (2009). Liquisolid Granulation Technique For Tablet Manufacturing: An Overview. Journal of Pharmacy Research
References
Baskaran M., Talluri K.B., Kuppusamy G., Karri V.V.S.R., & Kollipara R. (2016). Formulation Development of Atorvastatin Calcium Tablets by Gel Liquisolid Compact Technique for Improving Solid State Stability and Dissolution Profile. Journal of Drug Research and Development, 2(4), 1-7. https://dx.doi.org/10.16966/2470-1009.123
Chouksey R., Kumar Jain A., Pandey H., & Maithil A. (2011). Development and Bioavailability Studies of Atorvastatin Nanoemulsion. International Journal of Pharmacy & Life Sciences, 2(8), 982–988.
Gozali D., Putra A.F.C., & Sopyan I. (2014). Pengaruh Modifikasi Kristal Kalsium Atorvastatin Terhadap Laju Disolusi. Bionatura-Jurnal Ilmu-Ilmu Hayati dan Fisik, 16(2), 83–88.
Gozali D., Wardhana Y.W., & Shofa. (2015). Formulasi dan Evaluasi Tablet Dispersi Padat Kalsium Atorvastatin. Pharmascience, 2(2), 63–70.
Kadu P.J., Kushare S.S., Thacker D.D., & Gattani S.G. (2011). Enhancement of Oral Bioavailability of Atorvastatin Calcium by Self-Emulsifying Drug Delivery Systems (SEDDS). Pharmaceutical Development and Technology, 16(1), 65–74. https://doi.org/10.3109/10837450903499333
Khan F.N., & Dehghan M.H.G. (2011). Enhanced Bioavailability of Atorvastatin Calcium from Stabilized Gastric Resident Formulation. AAPS PharmSciTech, 12(4), 1077–1086. https://doi.org/10.1208/s12249-011-9673-3
Lu M., Xing H., Jiang J., Chen X., Yang T., Wang D., & Ding P. (2016). Liquisolid Technique and Its Applications in Pharmaceutics. Asian Journal of Pharmaceutical Sciences, 12(2), 115–123. https://doi.org/10.1016/j.ajps.2016.09.007
Oishi T.S., Nimmi I., & Islam S.M.A. (2011). Comparative In Vitro Bioequivalence Analysis of Some Generic Tablets of Atorvastatin, a BCS Class II Compound. Bangladesh Pharmaceutical Journal, 14(1), 61–66.
Panghal D., Nangpal M., Thakur G.S., & Arora S. (2014). Dissolution Improvement of Atorvastatin Calcium using Modified Locust Bean Gum by the Solid Dispersion Technique. Scientia Pharmaceutica, 82(1), 177–191. https://doi.org/10.3797/scipharm.1301-23
Patil P.R., Mahaparale P.R., & Shaikh K.U. (2021). Formulation, Development and Evaluation of Atorvastatin Ethosomal Gel. International Journal of Pharmaceutical Sciences and Research, 12(3), 1849–1859. https://doi.org/10.13040/IJPSR.0975-8232.12(3).1849-59
Popy F.A., Dewan I., Parvin M.N., & Islam S.M.A. (2012). Evaluation of In Vitro Equivalence for Tablets Containing the Poorly WaterSoluble Compound Atorvastatin. Dissolution Technologies, 19(4), 30–33.
Prabhu P., & Patravale V. (2015). Dissolution Enhancement of Atorvastatin Calcium by Co-Grinding Technique. Drug Delivery Translational Research, 6(4), 380–391. https://doi.org/10.1007/s13346-015-0271-x
Rodde M.S., Divase G.T., Devkar T.B., & Tekade A.R. (2014). Solubility and Bioavailability Enhancement of Poorly Aqueous Soluble Atorvastatin: In Vitro , Ex Vivo , and In Vivo Studies. Biomed Research International, 2014, 1–10. https://doi.org/10.1155/2014/463895
Sanjeev R., Gubbi, & Jarag, R. (2010). Formulation and Characterization of Atorvastatin Calcium Liquisolid Compacts. Asian Journal Pharmaceutical Sciences, 5(2), 50–60.
Snela A., Jadach B., Froelich A., Skotnicki M., Milczewska K., Rojewska M., Voelkel A., Prochaska K., & Lulek J. (2019). Self-Emulsifying Drug Delivery Systems with Atorvastatin Adsorbed on Solid Carriers: Formulation nd In Vitro Drug Release Studies. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 577, 281–290. https://doi.org/10.1016/j.colsurfa.2019.05.062
Sonje V.M., Kumar L., Meena C.L., Kohli G., Puri V., Jain R., Bansal A.K., & Brittain H.G. (2010). Atorvastatin Calcium. Profiles of Drug Substances, Excipients and Related Methodology, 35, 1-70. https://doi.org/10.1016/S1871-5125(10)35001-1
Spireas S. (1998). Liquisolid Systems and Methods of Preparing Same. Unites States Patent. 1–9.
Vraníková B., & Gajdziok J. (2013). Liquisolid Systems and Aspects Influencing Their Research and Development. Acta Pharmaceutica, 63, 447–465. https://doi.org/10.2478/acph-2013-0034
Vraníková B., Gajdziok J., & Vetchý D. (2015). Modern Evaluation of Liquisolid Systems with Varying Amounts of Liquid Phase Prepared Using Two Different Methods. Biomed Research International, 1–12. https://doi.org/10.1155/2015/608435
Wicaksono Y., Setyawan D., Siswandono S., & Siswoyo T.A. (2019). Preparation and Characterization of a Novel Cocrystal of Atorvastatin Calcium with Succinic Acid Coformer. Indonesian Journal of Chemistry, 19(3), 660-667. https://doi.org/10.22146/ijc.35801
Wicaksono Y., Wisudyaningsih B., & Siswoyo T.A. (2017). Enhancement of Solubility and Dissolution Rate of Atorvastatin Calcium by Co-Crystallization. Tropical Journal of Pharmaceutical Research, 16(7), 1497-1502. https://doi.org/10.4314/tjpr.v16i7.6
Windriyati Y.N., Badriyah M., Kusumaningtyas D.A., & Riesmalia R.L. (2020). Liquisolid Tablets Formulation of Atorvastatin Calcium Using Polyethylene Glycol 400 as Solvent and Some Carrier Materials. Indonesian Journal of Pharmacy, 31(4), 305–311. https://doi.org/10.22146/ijp.1138
Yadavb A.V., & Yardava V.B. (2009). Liquisolid Granulation Technique For Tablet Manufacturing: An Overview. Journal of Pharmacy Research