Solubility and Dissolution Enhancement of Dexibuprofen with Hydroxypropylbetacyclodextrin (HPβCD) and Poloxamers (188/407) Inclusion Complexes: Preparation and In Vitro Characterization

Rabia Munir¹, Abdul Hadi², Salah-Ud-Din Khan³, Sajid Asghar¹, Muhammad Irfan¹, Ikram Ullah Khan¹, Misbah Hameed⁴, Sana Inam¹, Nayyer Islam^{1

5}, Shahzadi Filza Hassan¹, Memoona Ishtiaq¹, Pervaiz Akhtar Shah⁶, Muhammad Shahid Iqbal⁷, Haroon Khalid Syed¹, Ahmed Khames⁸, Mohammad A S Abourehab^{9

10}

Affiliations

¹ Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad 38000, Pakistan.
² Department of Medicine, Xian Jiaotong University China, Xian 710000, China.
³ Department of Biochemistry, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11432, Saudi Arabia.
⁴ Institute of Pharmacy, Faculty of Pharmaceutical and Allied Health Sciences, Lahore College for Women University, Lahore 54000, Pakistan.
⁵ Department of Pharmacy, The University of Lahore, Lahore 54000, Pakistan.
⁶ University College of Pharmacy, University of the Punjab, Lahore 54590, Pakistan.
⁷ Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.
⁸ Department of Pharmaceutics and Industrial Pharmacy, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
⁹ Department of Pharmaceutics, Faculty of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia.
¹⁰ Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.

PMID: 35160569
PMCID: PMC8838044
DOI: 10.3390/polym14030579

Solubility and Dissolution Enhancement of Dexibuprofen with Hydroxypropylbetacyclodextrin (HPβCD) and Poloxamers (188/407) Inclusion Complexes: Preparation and In Vitro Characterization

Rabia Munir et al. Polymers (Basel). 2022.

. 2022 Jan 31;14(3):579.

doi: 10.3390/polym14030579.

Authors

Affiliations

¹ Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad 38000, Pakistan.
² Department of Medicine, Xian Jiaotong University China, Xian 710000, China.
³ Department of Biochemistry, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11432, Saudi Arabia.
⁴ Institute of Pharmacy, Faculty of Pharmaceutical and Allied Health Sciences, Lahore College for Women University, Lahore 54000, Pakistan.
⁵ Department of Pharmacy, The University of Lahore, Lahore 54000, Pakistan.
⁶ University College of Pharmacy, University of the Punjab, Lahore 54590, Pakistan.
⁷ Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.
⁸ Department of Pharmaceutics and Industrial Pharmacy, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
⁹ Department of Pharmaceutics, Faculty of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia.
¹⁰ Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.

PMID: 35160569
PMCID: PMC8838044
DOI: 10.3390/polym14030579

Abstract

The objective of this study was to improve the dissolution and solubility of dexibuprofen (DEX) using hydroxypropyl beta cyclodextrin (HPβCD) inclusion complexes and also to evaluate the effect of presence of hydrophilic polymers on solubilization efficiency of HPβCD. Three different methods (physical trituration, kneading and solvent evaporation) were used to prepare binary inclusion complexes at various drug-to-cyclodextrin weight ratios. An increase in solubility and drug release was observed with the kneading (KN) method at a DEX/HPβCD (1:4) weight ratio. The addition of hydrophilic polymers poloxamer-188 (PXM-188) and poloxamer-407 (PXM-407) at 2.5, 5.0, 10.0 and 20% w/w enhanced the complexation efficiency and solubility of DEX/HPβCD significantly. Fourier-transform infrared (FTIR) analysis revealed that DEX was successfully incorporated into the cyclodextrin cavity. Differential scanning calorimetry (DSC) and X-ray diffractometry (XRD) revealed less crystallinity of the drug and its entrapment in the cyclodextrin molecular cage. The addition of PXM-188 or PXM-407 reduced the strength of the DEX endothermic peak. With the addition of hydrophilic polymers, sharp and intense peaks of DEX disappeared. Finally, it was concluded that PXM-188 at a weight ratio of 10.0% w/w was the best candidate for improving solubility, stability and release rate of DEX.

Keywords: HPβCD; PXM; dexibuprofen; inclusion complex.

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Conflict of interest statement

There is no conflict of interest for any of the listed authors.

Figures

**Figure 1**
Chemical structure of (A) DEX, (B) HPβCD and (C) poloxamers. Note: x, y and z are hydrophilic ethyleneoxide (EO), hydrophobic propyleneoxide (PO) and hydrophilic (EO) units.

**Figure 2**
(A) Phase solubility diagram of DEX in aqueous solution of HPβCD mean ± SD, n = 3. (B) Phase solubility diagram of DEX in aqueous solution of HPβCD with/without PXM−188. (C) Phase solubility diagram of DEX in aqueous solution of HPβCD with/without PXM−407.

**Figure 3**
(A) Dissolution profiles of DEX and DEX–HPβCD inclusion complexes by PT method Mean ± SD, n = 3. (B) Dissolution profiles of DEX and DEX–HPβCD inclusion complexes by KN Mean ± SD, n = 3. (C) Dissolution profiles of DEX and DEX–HPβCD inclusion complexes SE method. Mean ± SD, n = 3. (D) Dissolution profiles of DEX, binary system and DEX:HPβCD ternary systems with PXM-188. Mean ± SD, n = 3. (E) Dissolution profiles of DEX, binary system DEX:HPβCD and ternary systems with PXM-407. Mean ± SD, n = 3.

**Figure 4**
(A) SEM pictures of (a) DEX, (b)HPβCD and (c) 1:4 DEX:HPβCD. (B) SEM pictures of (a) DEX, (b) PXM-188, (c), 1:4 DEX:HPβCD:PXM-188 2.5%, (d) 1:4 DEX:HPβCD:PXM-188 5.0%, (e) 1:4 DEX:HPβCD:PXM-188 10% and (f) 1:4 DEX:HPβCD:PXM-188 20%. (C) SEM pictures of (a) DEX, (b) PXM-407, (c) 1:4 DEX:HPβCD:PXM-407 2.5%, (d) 1:4 DEX:HPβCD:PXM-407 5.0%, (e) 1:4 DEX:HPβCD:PXM-407 10% and (f) 1:4 DEX:HPβCD:PXM-407 20%.

**Figure 5**
(A) FTIR spectrum of (a) DEX, (b) HPβCD, (c) DEX/HPβCD (1:1), (d) DEX/HPβCD (1:2) and (e) DEX/HPβCD (1:4) prepared by kneading method. (B) FTIR spectrum of (a) DEX, (b) PXM−188, (c) 1:4 DEX:HPβCD, (d) 1:4 DEX:HPβCD:PXM−188 2.5%, (e) 1:4 DEX:HPβCD:PXM−188 5.0%, (f) 1:4 DEX:HPβCD:PXM−188 10% and (g) 1:4 DEX:HPβCD:PXM−188 20%. (C) FTIR spectrum of (a) DEX, (b) PXM−407, (c), 1:4 DEX:HPβCD, (d) 1:4 DEX:HPβCD:PXM−407 2.5%, (e) 1:4 DEX:HPβCD:PXM−407 5.0%, (f) 1:4 DEX:HPβCD:PXM−407 10% and (f) 1:4 DEX:HPβCD:PXM−407 20%.

**Figure 6**
(A) DSC thermo-grams of (a) DEX, (b) PXM−188, (c), 1:4 DEX:HPβCD (d) 1:4 DEX:HPβCD:PXM−188 2.5%, (e) 1:4 DEX:HPβCD:PXM-188 5.0%, (f) 1:4 DEX:HPβCD:PXM−188 10% and (g) DEX:HPβCD:PXM−188 20%. (B) DSC thermo-grams of (a) DEX, (b) PXM−407, (c), 1:4 DEX:HPβCD, (d) 1:4 DEX:HPβCD:PXM−407 2.5%, (e) 1:4 DEX:HPβCD:PXM−407 5.0%, (f) 1:4 DEX:HPβCD:PXM4−07 10% and (g) 1:4 DEX:HPβCD:PXM−407 20%.

**Figure 7**
(A) XRD Diffractrograms of (a) DEX, (b) PXM-188, (c), 1:4 DEX:HPβCD, (d) 1:4 DEX:HPβCD:PXM-188 2.5%, (e) 1:4 DEX:HPβCD:PXM-188 5.0%, (f) 1:4 DEX:HPβCD:PXM-188 10% and (g) 1:4 DEX:HPβCD:PXM-188 20%. (B) XRD Diffractrograms of (a) DEX, (b) PXM-407, (c), 1:4 DEX:HPβCD, (d) 1:4 DEX:HPβCD:PXM-407 2.5%, (e) 1:4 DEX:HPβCD:PXM-407 5.0%, (f) 1:4 DEX:HPβCD:PXM-407 10% and (g) 1:4 DEX:HPβCD:PXM-407 20%.

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Solubility and Dissolution Enhancement of Dexibuprofen with Hydroxypropylbetacyclodextrin (HPβCD) and Poloxamers (188/407) Inclusion Complexes: Preparation and In Vitro Characterization

Affiliations

Solubility and Dissolution Enhancement of Dexibuprofen with Hydroxypropylbetacyclodextrin (HPβCD) and Poloxamers (188/407) Inclusion Complexes: Preparation and In Vitro Characterization

Authors

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Abstract

Conflict of interest statement

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