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Formulation Development and In-Vitro Characterization of Liquid and Solid Self Microemulsifying Drug Delivery System of Apremilast
Corresponding Author(s) : Umamaheswari.D
International Journal of Allied Medical Sciences and Clinical Research,
Vol. 13 No. 2 (2025): 2025 Volume -13 - Issue 2
Abstract
Background: Most drugs are administered orally, but this route is limited for molecules with poor aqueous solubility, a key factor in achieving effective systemic drug concentrations for the desired pharmacological response. Many potential drugs face low solubility and dissolution rates, reducing absorption and low oral bioavailability.
Objective: This study focused on developing and evaluating liquid (L-SMEDDS) and solid (S-SMEDDS) self-microemulsifying drug delivery systems for the poorly water-soluble Apremilast. The L-SMEDDS formulation used oleic acid (oil), Tween 80 (surfactant), and Transcutol HP (co-surfactant). S-SMEDDS were prepared via adsorption onto Aerosil as a solid carrier. L-SMEDDS were assessed for self-emulsification time, droplet size, zeta potential, PDI, transmittance, and drug content. S-SMEDDS evaluations included micromeritic properties, drug content, in vitro release, and structural analysis via SEM, DSC, and XRD.
Result: The findings showed that solid SMEDDS significantly enhanced the dissolution rate of Apremilast, improving bioavailability by forming a microemulsion upon dilution in gastric fluids, which promotes better drug release.
Conclusion: Overall, the results indicate that solid SMEDDS can significantly improve the solubility and dissolution profile of poorly soluble drugs, offering potential to enhance oral bioavailability and therapeutic efficacy.
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- Pande SV, Biyani KR, Microencapsulation by solvent evaporation method of BCS Class 4 drugs for bioavailability enhancement. Journal of Drug Delivery and Therapeutics. 2016; 6(5):18-30.
- Mundhe AV, Fuloria NK, Biyani KR, Co crystallization: an alternative approach for solid modification. Journal of Drug Delivery and Therapeutics. 2013; 3(4):166-172.
- Shelke PV, Dumbare AS, Gadhave MV, Jadhav SL, Sonawane AA, Gaikwad DD, Formulation and evaluation of rapidly dis integrating film of amlodipine besylate, Journal of Drug Delivery & Therapeutics. 2012; 2(2):72-75.
- Abdalla A, Sandra K, Mader K. A new self-emulsifying drug delivery system (SEDDS) for poorly soluble drugs: characterization, dissolution, in vitro digestion and incorporation into solid pellets. Eur J Pharm Sci. 2008; 35(5):457-464.
- Pouton CW. Formulation of poorly water-soluble drugs for oral administration: physicochemical and physiological issues and the lipid formulation classification system. Eur J Pharm Sci. 2006; 29(4): 278- 287.
- Chandel P, Kumari R, Kapoor A, Liquisolid technique: an approach for enhancement of solubility, Journal of drug delivery and therapeutics. 2013; 3(4):131-137.
- Miryala V, Kurakula M, Self-nano emulsifying drug delivery systems (SNEDDS) for oral delivery of atorvastatin– formulation and bioavailability studies. Journal of Drug Delivery & Therapeutics. 2013; 3(3):131-142.
- Singh J, Walia M, Harikumar SL, Solubility enhancement by solid dispersion method: a review. Journal of drug delivery and Therapeutics. 2013; 3(5):148-155.
- Dalvi PB, Gerange AB, Ingale PR, Solid dispersion: strategy to enhance solubility, Journal of Drug Delivery and Therapeutics. 2015; 5(2):20-28.
- Aungst BJ. Novel formulation strategies for improving oral bioavailability of drugs with poor membrane permeation or presystemic metabolism. J Pharm Sci. 1993; 82:979-987.
- Shah DP, Patel B, Shah C, Nanosuspension technology: A innovative slant for drug delivery system and permeability enhancer for poorly water-soluble drugs. Journal of Drug Delivery and Therapeutics. 2015; 5(1):10-23.
- Murdandea SB, Gumkowskia MJ. Development of a self-emulsifying formulation that reduces the food effect of torcetrapib. Int J of Pharm. 2008; 351: 15-22.
- Venkatesh, G. et al. In vitro and in vivo evaluation of self-micro emulsifying drug delivery system of buparvaquone. Drug Dev. Ind. Pharm. 2010; 36:735–745.
- Gursoy, R.N. and Benita, S. Self-emulsifying drug delivery systems (SEDDS) for improved oral delivery of lipophilic drugs. Biomed. Pharmacother. 2004; 58:173–182.
- Singh, B. et al. Self-emulsifying drug delivery systems (SEDDS): formulation development, characterization, and applications. Crit. Rev. Ther. Drug Carrier Syst. 2009; 26:427–521.
- Charman WN, Stella VJ. Transport of lipophilic molecules by the intestinal lymphatic system. Adv Drug Del Rev. 1991; 7:1- 14.
- Porter CJ, Trevaskis NL, Charman WN. Lipids and lipid-based formulations: optimizing the oral delivery of lipophilic drugs. Nat Rev Drug Discovery. 2007; 6:231-248.
- Sanghai B, Aggarwal G, Hari Kumar SL, Solid self-micro emulsifying drug delivery system: a review. Journal of Drug Delivery and Therapeutics. 2013; 3 (3):168-174.
- Hemanth Palepu, Sai Prasanna Prathipati. Enhancement of solubility and dissolution rate of apremilast by recrystallization technique. International journal of research in pharmacy and chemistry, 2019:9(3):161-170.
- Sanjesh Rathi, Dhaval Patel. Formulation Development and In-vitro Evaluation of Apremilast Floating Tablet. Der Pharma Chemica, 2022:14(8):01-10.
- Madhura Mestry, Dr. Meenal Rane Dr. Pramod Kadu, Snehal More. Self- emulsifying Drug Delivery System of Rosuvastatin Calcium. International Journal of Pharmacy, 2017(4): 130-139.
- Vipul Rokad, Chirag Nagda and Dhruti Nagda. Design and evaluation of solid self- emulsifying drug delivery system of rosuvastatin calcium. Journal of Young Pharmacists, Jul-Sep 2014: 6 (3): 444-449.
- Maria Saifee, Pragati Bhaske, and Reshma Toshniwal. Formulation and optimization of simvastatin loaded microemulsion based gel: Invitro characterization. International Research Journal of Pharmacy, 2021: 12 (7): 21-27.
- Murat Sami Berkman1 and Kadri Gulec. Pseudo ternary phase diagrams: a practical approach for the area and centroid calculation of stable microemulsion regions. Istanbul Journal Pharmacy,2020: 51 (1): 42-49.
- Sachan R, Khatri K, Kasture S. Self- Emulsifying Drug Delivery System: A Novel Approach for enhancement of Bioavailability. Int J PharmTech,2010:2(3):1738-45.
- Khoo SM, Humberstone AJ, Porter CJH, Edward GA, Charman WN. Formulation Design and bioavailability assessment of lipidic self-emulsifying formulation of halofantrine. Int J Pharm 1998; 167:155-64.
- Foram Contractor, Kantilal Narkhede and Anuradha Prajapat. Formulation development and evaluation of solid self microemulsifying drug delivery system to enhance solubility of vorapaxar. World Journal of Pharmaceutical and Medical Research, 2024:10(8):131-143.
- Anuradha P. Prajapati, Pratik S. Patel, Neha S. Vadgama. Formulation Development and Evaluation of Solid Self Microemulsifying Drug Delivery System of Azelnidipine. International Journal of Pharmaceutical Sciences and Drug Research, 2023:15(3):237-249.
- Ratna Sree Vadapalli, Sunitha Reddy. Formulation and Evaluation of Self-Micro Emulsifying Drug Delivery System (SMEDDS) of Ticagrelor. Saudi Journal of Medical and Pharmaceutical Sciences, 2022: 8(11): 628-643.
- Parul Jaiswal, Geeta Aggarwal. Development of self-microemulsifying drug delivery system and solid-self-microemulsifying drug delivery system of telmisartan. International Journal of Pharmaceutical Investigation 2014: 4(4):195–206.
- Shrinivas Pachaval, Satish Puttachari, Arshia Shariff, Thakur RS. Formulation and Evaluation of Solid Self-microemulsifying Drug Delivery System of a Selective Second-Generation Cephalosporin Antibiotic. International Journal of Pharmaceutical Sciences Review and Research 2014: 24(2): 176-181.
- Indian Pharmacopoeia. Apremilast and Apremilast Tablet, 2022: 2: 1489-1492.
- Hatefi A, Amsden B, Biodegradable in-situ gel forming drug delivery system. Journal of controlled release. 2002; 47: 9-28.
- Sing k, Harikumar S L. Injectable in-situ gelling controlled release drug delivery system. International journal of drug development and research. 2012; 12: 1-18.
- Suvakanta Dash, Padala Narasimha Murthy, Lilakanta Nath and Prasanta Chowdhury. Kinetic Modeling on Drug Release from Controlled Drug Delivery Systems, Acta Poloniae Pharmaceuticals- Drug Research,67 (3), 2010; PP 217-223.
- Brahmankar DM, Sunil B, Jaiswal. Text Book Biopharmaceutics and Pharmacokinetics - A Treatise. 2nd Ed. New Delhi: Jaypee Publishers; 2002. P. 400- 443.
- Jameer A Tamboli, Shrinivas K Mohite. Development of solid self-microemulsifying drug delivery system of diacerein for enhanced dissolution rate. Asian journal of pharmaceutical and clinical research. 2019: 12(2):315-319.
- Mukesh P. Ratnaparkhi, Praveen D. Chaudhari. Design, development and characterization of self-micro emulsifying drug delivery system for aceclofenac. International Journal of Pharmaceutical Sciences and Research, 2018; Vol. 9(9): 3815-3826.
- Dong Shik Kim, Jung Hyun Cho. Self-microemulsifying drug delivery system (SMEDDS) for improved oral delivery and photostability of methotrexate. International Journal of Nanomedicine. 2019:14:4949–4960.
- Pankaj Laddha, Vrunda Suthar, Shital Butani. Development and optimization of self microemulsifying drug delivery of domperidone. Brazilian Journal of Pharmaceutical Sciences. 2014: 50: 91-100.
References
Pande SV, Biyani KR, Microencapsulation by solvent evaporation method of BCS Class 4 drugs for bioavailability enhancement. Journal of Drug Delivery and Therapeutics. 2016; 6(5):18-30.
Mundhe AV, Fuloria NK, Biyani KR, Co crystallization: an alternative approach for solid modification. Journal of Drug Delivery and Therapeutics. 2013; 3(4):166-172.
Shelke PV, Dumbare AS, Gadhave MV, Jadhav SL, Sonawane AA, Gaikwad DD, Formulation and evaluation of rapidly dis integrating film of amlodipine besylate, Journal of Drug Delivery & Therapeutics. 2012; 2(2):72-75.
Abdalla A, Sandra K, Mader K. A new self-emulsifying drug delivery system (SEDDS) for poorly soluble drugs: characterization, dissolution, in vitro digestion and incorporation into solid pellets. Eur J Pharm Sci. 2008; 35(5):457-464.
Pouton CW. Formulation of poorly water-soluble drugs for oral administration: physicochemical and physiological issues and the lipid formulation classification system. Eur J Pharm Sci. 2006; 29(4): 278- 287.
Chandel P, Kumari R, Kapoor A, Liquisolid technique: an approach for enhancement of solubility, Journal of drug delivery and therapeutics. 2013; 3(4):131-137.
Miryala V, Kurakula M, Self-nano emulsifying drug delivery systems (SNEDDS) for oral delivery of atorvastatin– formulation and bioavailability studies. Journal of Drug Delivery & Therapeutics. 2013; 3(3):131-142.
Singh J, Walia M, Harikumar SL, Solubility enhancement by solid dispersion method: a review. Journal of drug delivery and Therapeutics. 2013; 3(5):148-155.
Dalvi PB, Gerange AB, Ingale PR, Solid dispersion: strategy to enhance solubility, Journal of Drug Delivery and Therapeutics. 2015; 5(2):20-28.
Aungst BJ. Novel formulation strategies for improving oral bioavailability of drugs with poor membrane permeation or presystemic metabolism. J Pharm Sci. 1993; 82:979-987.
Shah DP, Patel B, Shah C, Nanosuspension technology: A innovative slant for drug delivery system and permeability enhancer for poorly water-soluble drugs. Journal of Drug Delivery and Therapeutics. 2015; 5(1):10-23.
Murdandea SB, Gumkowskia MJ. Development of a self-emulsifying formulation that reduces the food effect of torcetrapib. Int J of Pharm. 2008; 351: 15-22.
Venkatesh, G. et al. In vitro and in vivo evaluation of self-micro emulsifying drug delivery system of buparvaquone. Drug Dev. Ind. Pharm. 2010; 36:735–745.
Gursoy, R.N. and Benita, S. Self-emulsifying drug delivery systems (SEDDS) for improved oral delivery of lipophilic drugs. Biomed. Pharmacother. 2004; 58:173–182.
Singh, B. et al. Self-emulsifying drug delivery systems (SEDDS): formulation development, characterization, and applications. Crit. Rev. Ther. Drug Carrier Syst. 2009; 26:427–521.
Charman WN, Stella VJ. Transport of lipophilic molecules by the intestinal lymphatic system. Adv Drug Del Rev. 1991; 7:1- 14.
Porter CJ, Trevaskis NL, Charman WN. Lipids and lipid-based formulations: optimizing the oral delivery of lipophilic drugs. Nat Rev Drug Discovery. 2007; 6:231-248.
Sanghai B, Aggarwal G, Hari Kumar SL, Solid self-micro emulsifying drug delivery system: a review. Journal of Drug Delivery and Therapeutics. 2013; 3 (3):168-174.
Hemanth Palepu, Sai Prasanna Prathipati. Enhancement of solubility and dissolution rate of apremilast by recrystallization technique. International journal of research in pharmacy and chemistry, 2019:9(3):161-170.
Sanjesh Rathi, Dhaval Patel. Formulation Development and In-vitro Evaluation of Apremilast Floating Tablet. Der Pharma Chemica, 2022:14(8):01-10.
Madhura Mestry, Dr. Meenal Rane Dr. Pramod Kadu, Snehal More. Self- emulsifying Drug Delivery System of Rosuvastatin Calcium. International Journal of Pharmacy, 2017(4): 130-139.
Vipul Rokad, Chirag Nagda and Dhruti Nagda. Design and evaluation of solid self- emulsifying drug delivery system of rosuvastatin calcium. Journal of Young Pharmacists, Jul-Sep 2014: 6 (3): 444-449.
Maria Saifee, Pragati Bhaske, and Reshma Toshniwal. Formulation and optimization of simvastatin loaded microemulsion based gel: Invitro characterization. International Research Journal of Pharmacy, 2021: 12 (7): 21-27.
Murat Sami Berkman1 and Kadri Gulec. Pseudo ternary phase diagrams: a practical approach for the area and centroid calculation of stable microemulsion regions. Istanbul Journal Pharmacy,2020: 51 (1): 42-49.
Sachan R, Khatri K, Kasture S. Self- Emulsifying Drug Delivery System: A Novel Approach for enhancement of Bioavailability. Int J PharmTech,2010:2(3):1738-45.
Khoo SM, Humberstone AJ, Porter CJH, Edward GA, Charman WN. Formulation Design and bioavailability assessment of lipidic self-emulsifying formulation of halofantrine. Int J Pharm 1998; 167:155-64.
Foram Contractor, Kantilal Narkhede and Anuradha Prajapat. Formulation development and evaluation of solid self microemulsifying drug delivery system to enhance solubility of vorapaxar. World Journal of Pharmaceutical and Medical Research, 2024:10(8):131-143.
Anuradha P. Prajapati, Pratik S. Patel, Neha S. Vadgama. Formulation Development and Evaluation of Solid Self Microemulsifying Drug Delivery System of Azelnidipine. International Journal of Pharmaceutical Sciences and Drug Research, 2023:15(3):237-249.
Ratna Sree Vadapalli, Sunitha Reddy. Formulation and Evaluation of Self-Micro Emulsifying Drug Delivery System (SMEDDS) of Ticagrelor. Saudi Journal of Medical and Pharmaceutical Sciences, 2022: 8(11): 628-643.
Parul Jaiswal, Geeta Aggarwal. Development of self-microemulsifying drug delivery system and solid-self-microemulsifying drug delivery system of telmisartan. International Journal of Pharmaceutical Investigation 2014: 4(4):195–206.
Shrinivas Pachaval, Satish Puttachari, Arshia Shariff, Thakur RS. Formulation and Evaluation of Solid Self-microemulsifying Drug Delivery System of a Selective Second-Generation Cephalosporin Antibiotic. International Journal of Pharmaceutical Sciences Review and Research 2014: 24(2): 176-181.
Indian Pharmacopoeia. Apremilast and Apremilast Tablet, 2022: 2: 1489-1492.
Hatefi A, Amsden B, Biodegradable in-situ gel forming drug delivery system. Journal of controlled release. 2002; 47: 9-28.
Sing k, Harikumar S L. Injectable in-situ gelling controlled release drug delivery system. International journal of drug development and research. 2012; 12: 1-18.
Suvakanta Dash, Padala Narasimha Murthy, Lilakanta Nath and Prasanta Chowdhury. Kinetic Modeling on Drug Release from Controlled Drug Delivery Systems, Acta Poloniae Pharmaceuticals- Drug Research,67 (3), 2010; PP 217-223.
Brahmankar DM, Sunil B, Jaiswal. Text Book Biopharmaceutics and Pharmacokinetics - A Treatise. 2nd Ed. New Delhi: Jaypee Publishers; 2002. P. 400- 443.
Jameer A Tamboli, Shrinivas K Mohite. Development of solid self-microemulsifying drug delivery system of diacerein for enhanced dissolution rate. Asian journal of pharmaceutical and clinical research. 2019: 12(2):315-319.
Mukesh P. Ratnaparkhi, Praveen D. Chaudhari. Design, development and characterization of self-micro emulsifying drug delivery system for aceclofenac. International Journal of Pharmaceutical Sciences and Research, 2018; Vol. 9(9): 3815-3826.
Dong Shik Kim, Jung Hyun Cho. Self-microemulsifying drug delivery system (SMEDDS) for improved oral delivery and photostability of methotrexate. International Journal of Nanomedicine. 2019:14:4949–4960.
Pankaj Laddha, Vrunda Suthar, Shital Butani. Development and optimization of self microemulsifying drug delivery of domperidone. Brazilian Journal of Pharmaceutical Sciences. 2014: 50: 91-100.