Supersaturated Gel Formulation (SGF) of Atorvastatin at a Maximum Dose of 80 mg with Enhanced Solubility, Dissolution, and Physical Stability
The objective of this work was to develop a supersaturated gel formulation (SGF) loaded with the maximum atorvastatin calcium trihydrate (ATR) dose. The maximum dose strength of ATR needs to be reduced through improving solubility and dissolution rate to mitigate side effects due to the necessity of...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-12-01
|
| Series: | Gels |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2310-2861/10/12/837 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850241046620930048 |
|---|---|
| author | Jin Woo Park Sa-Won Lee Jun Hak Lee Sung Mo Park Sung Jun Cho Han-Joo Maeng Kwan Hyung Cho |
| author_facet | Jin Woo Park Sa-Won Lee Jun Hak Lee Sung Mo Park Sung Jun Cho Han-Joo Maeng Kwan Hyung Cho |
| author_sort | Jin Woo Park |
| collection | DOAJ |
| description | The objective of this work was to develop a supersaturated gel formulation (SGF) loaded with the maximum atorvastatin calcium trihydrate (ATR) dose. The maximum dose strength of ATR needs to be reduced through improving solubility and dissolution rate to mitigate side effects due to the necessity of taking high doses. ATR has highly pH-dependent solubility at 37 °C, leading to poor solubility (<10 μg/mL) in stomach acid (pH 1.2). Among the various molecular weights of polyethylene glycols (PEGs) and surfactants, PEG 200 and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) were selected as the solubilizer and precipitation inhibitor for ATR, respectively. PEG 200 demonstrated very high solubility for ATR (>60%, <i>w</i>/<i>w</i>), and the combined use of TPGS and PEG 200 formed an organogel state and suppressed ATR precipitation, showing 15-fold higher dispersion solubility in buffer solution at pH 1.2 compared to the formulation with PEG 200 alone. The optimal SGF composition (ATR/PEG 200/TPGS = 10/60/30, <i>w</i>/<i>w</i>) exhibited an over 95% dissolution rate within 2 h at pH 1.2, compared to less than 50% for the original commercial product. In a transmission electron microscope analysis, the SGF suppressed ATR precipitation and revealed smaller precipitated particles (<300 nm) compared to the control samples. In the XRD analysis, the SGF was physically stable for 100 days at room temperature without the recrystallization of ATR. In conclusion, the SGF suggested in this work would be an alternative formulation for the treatment of dyslipidemia with enhanced solubility, dissolution, and physical stability. |
| format | Article |
| id | doaj-art-cdd4dfd884b045379cdd4691607051a8 |
| institution | OA Journals |
| issn | 2310-2861 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Gels |
| spelling | doaj-art-cdd4dfd884b045379cdd4691607051a82025-08-20T02:00:42ZengMDPI AGGels2310-28612024-12-01101283710.3390/gels10120837Supersaturated Gel Formulation (SGF) of Atorvastatin at a Maximum Dose of 80 mg with Enhanced Solubility, Dissolution, and Physical StabilityJin Woo Park0Sa-Won Lee1Jun Hak Lee2Sung Mo Park3Sung Jun Cho4Han-Joo Maeng5Kwan Hyung Cho6College of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, 197 Inje-ro, Gimhae 50834, Republic of KoreaDepartment of Pharmaceutical Engineering, Inje University, 197 Inje-ro, Gimhae 50834, Republic of KoreaCollege of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, 197 Inje-ro, Gimhae 50834, Republic of KoreaCollege of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, 197 Inje-ro, Gimhae 50834, Republic of KoreaDepartment of Anesthesiology, National Medical Center, 245 Eulji-ro, Seoul 04564, Republic of KoreaCollege of Pharmacy, Gachon University, 191 Hambakmoei-ro, Yeonsu-gu, Incheon 21936, Republic of KoreaCollege of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, 197 Inje-ro, Gimhae 50834, Republic of KoreaThe objective of this work was to develop a supersaturated gel formulation (SGF) loaded with the maximum atorvastatin calcium trihydrate (ATR) dose. The maximum dose strength of ATR needs to be reduced through improving solubility and dissolution rate to mitigate side effects due to the necessity of taking high doses. ATR has highly pH-dependent solubility at 37 °C, leading to poor solubility (<10 μg/mL) in stomach acid (pH 1.2). Among the various molecular weights of polyethylene glycols (PEGs) and surfactants, PEG 200 and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) were selected as the solubilizer and precipitation inhibitor for ATR, respectively. PEG 200 demonstrated very high solubility for ATR (>60%, <i>w</i>/<i>w</i>), and the combined use of TPGS and PEG 200 formed an organogel state and suppressed ATR precipitation, showing 15-fold higher dispersion solubility in buffer solution at pH 1.2 compared to the formulation with PEG 200 alone. The optimal SGF composition (ATR/PEG 200/TPGS = 10/60/30, <i>w</i>/<i>w</i>) exhibited an over 95% dissolution rate within 2 h at pH 1.2, compared to less than 50% for the original commercial product. In a transmission electron microscope analysis, the SGF suppressed ATR precipitation and revealed smaller precipitated particles (<300 nm) compared to the control samples. In the XRD analysis, the SGF was physically stable for 100 days at room temperature without the recrystallization of ATR. In conclusion, the SGF suggested in this work would be an alternative formulation for the treatment of dyslipidemia with enhanced solubility, dissolution, and physical stability.https://www.mdpi.com/2310-2861/10/12/837atorvastatin calciumorganogel formulationdissolutionsolubilityphysical stability |
| spellingShingle | Jin Woo Park Sa-Won Lee Jun Hak Lee Sung Mo Park Sung Jun Cho Han-Joo Maeng Kwan Hyung Cho Supersaturated Gel Formulation (SGF) of Atorvastatin at a Maximum Dose of 80 mg with Enhanced Solubility, Dissolution, and Physical Stability Gels atorvastatin calcium organogel formulation dissolution solubility physical stability |
| title | Supersaturated Gel Formulation (SGF) of Atorvastatin at a Maximum Dose of 80 mg with Enhanced Solubility, Dissolution, and Physical Stability |
| title_full | Supersaturated Gel Formulation (SGF) of Atorvastatin at a Maximum Dose of 80 mg with Enhanced Solubility, Dissolution, and Physical Stability |
| title_fullStr | Supersaturated Gel Formulation (SGF) of Atorvastatin at a Maximum Dose of 80 mg with Enhanced Solubility, Dissolution, and Physical Stability |
| title_full_unstemmed | Supersaturated Gel Formulation (SGF) of Atorvastatin at a Maximum Dose of 80 mg with Enhanced Solubility, Dissolution, and Physical Stability |
| title_short | Supersaturated Gel Formulation (SGF) of Atorvastatin at a Maximum Dose of 80 mg with Enhanced Solubility, Dissolution, and Physical Stability |
| title_sort | supersaturated gel formulation sgf of atorvastatin at a maximum dose of 80 mg with enhanced solubility dissolution and physical stability |
| topic | atorvastatin calcium organogel formulation dissolution solubility physical stability |
| url | https://www.mdpi.com/2310-2861/10/12/837 |
| work_keys_str_mv | AT jinwoopark supersaturatedgelformulationsgfofatorvastatinatamaximumdoseof80mgwithenhancedsolubilitydissolutionandphysicalstability AT sawonlee supersaturatedgelformulationsgfofatorvastatinatamaximumdoseof80mgwithenhancedsolubilitydissolutionandphysicalstability AT junhaklee supersaturatedgelformulationsgfofatorvastatinatamaximumdoseof80mgwithenhancedsolubilitydissolutionandphysicalstability AT sungmopark supersaturatedgelformulationsgfofatorvastatinatamaximumdoseof80mgwithenhancedsolubilitydissolutionandphysicalstability AT sungjuncho supersaturatedgelformulationsgfofatorvastatinatamaximumdoseof80mgwithenhancedsolubilitydissolutionandphysicalstability AT hanjoomaeng supersaturatedgelformulationsgfofatorvastatinatamaximumdoseof80mgwithenhancedsolubilitydissolutionandphysicalstability AT kwanhyungcho supersaturatedgelformulationsgfofatorvastatinatamaximumdoseof80mgwithenhancedsolubilitydissolutionandphysicalstability |