Intestinal Absorption Study: Challenges and Absorption Enhancement Strategies in Improving Oral Drug Delivery
Abstract
1. Introduction
2. The Challenges in Oral Drug Delivery
2.1. Mucous
2.2. Tight Junction
2.3. Efflux Transporters
2.4. Enzymes
2.5. First-Pass Metabolism
2.6. Intestinal Lymphatic Transport
3. Current Absorption Enhancers and Their Absorption-Enhancing Mechanisms to Improve the Pharmacokinetic Profile
3.1. Solubilizing Agents
3.2. Bile Salts
Drug (s) | Absorption Enhancer | Model | Results | Ref. |
---|---|---|---|---|
5(6)-carboxyfluorescein | Sodium glycocholate (SGC) and sodium taurodeoxycholate (STDC) | In vitro: Caco-2 cell | SGC was a slightly better absorption enhancer for the 5(6)-carboxyfluorescein than STDC but not significant (p > 0.05). | [73] |
Cefquinome | Sodium taurocholate | In vitro: Caco-2 cell | At 2 mmol/L sodium taurocholate, the transportation of cefquinome substantially increased. | [72] |
In vivo: rat intestine | At 10 and 20 mmol/L sodium taurocholate, the absorption of the drug increased in a concentration-dependent manner. | |||
Berberine chloride | Sodium deoxycholate | In vivo: rat intestine | AUC0–36h: 35.3-fold increase | [70] |
Gliclazide | Taurocholic acid | In vivo: rat intestine | The microcapsules containing taurocholic acid increased the gliclazide absorption (p < 0.01). | [71] |
EGFR2R-lytic hybrid peptide | Sodium taurodeoxycholate | In vitro: Caco-2 cell | Papp: 5.0-fold increase | [74] |
3.3. Chitosan
Drug (s) | Absorption Enhancer | Model | Results | Ref. |
---|---|---|---|---|
Acyclovir | Chitosan | In vitro: Caco-2 cell | Papp: 124- and 143-fold increase | [83] |
In vivo: rat intestine | AUC0–12 and AUC0–∞: 0.70- and 0.74-fold decrease Cmax: 0.56- and 0.63-fold decrease Tmax: 1.25- and 1.50-fold increase | |||
In vitro: Ussing chamber | Papp: 1.08- and 2.33-fold increase | |||
Glucosamine hydrochloride | Chitosan | In vitro: Caco-2 cell | Papp: 1.9, 2.5 and 4.0-fold increase | [88] |
In vivo: rat intestine | Cmax: 2.8-fold increase Tmax: no change AUC0−∞: 2.5-fold increase | |||
Salvianolic acid B | Chitosan | In vitro: Caco-2 cell | Papp: 4.43-fold increase | [79] |
In vivo: rat intestine | AUC0–∞: 4.25-fold increase | |||
Berberine | Chitosan hydrochloride | In vivo: rat intestine | AUC0–36: no improvement Cmax: no improvement | [86] |
Chitosan | In vivo: rat intestine | AUC0–36: maximum 2.5-fold increase | ||
Amphotericin B | Trimethyl chitosan | In vitro: Caco-2 cell | Papp: 1.11-fold increase | [87] |
4. Formulation Strategies to Improve Pharmacokinetics Profile
4.1. Solid Lipid Nanoparticles (SLN)
4.2. Dimers
Drug (s) | Model | Results | Ref. |
---|---|---|---|
5(6)-carboxyfluorescein (CF), fluorescein isothiocyanate-labeled dextrans (FD4, FD10) and alendronate | In vitro: diffusion chamber | Papp: increased except for FD10. | [98] |
In vivo: rat intestine | The greatest AUC achieved in the presence of Ac50-G2 (0.5%, w/v). | ||
Camptothecin | In vivo: rat intestine | AUC: 2- to 3-fold increase Cmax: increased Tmax: no change | [100] |
Simvastatin | In vivo: rat intestine | AUC: increased Cmax: increased Tmax: 1.5-fold increase | [99] |
In vitro: Caco-2 cell | Papp: increased | ||
Propranolol | In vitro Release Study (dialysis sac) | Papp: increased | [102] |
In vitro: Caco-2 cell | AUC: increased | [101] |
4.3. Nanoemulsions
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Drug (s) | Absorption Enhancer | Model | Results | Ref. |
---|---|---|---|---|
[14C]-mannitol | Sucrose laurate | In vitro: Caco-2 cell | Papp: 9-fold increase | [57] |
Sucrose laurate | In vitro: Ussing chamber | Papp: 2.6-fold increase | ||
Insulin | Sucrose laurate | In situ: rat jejunum and colon | Relative bioavailability (F, %): 8.9% increase | [57] |
Fluorescein, atenolol, rhodamine 123, and vinblastine | Sucrose laurate | In vitro: Caco-2 cell | Papp: several folds increase for all drugs. | [65] |
Carbamazepine | Cyclodextrins | In vivo: dogs | Tmax: 0.6-fold decrease Cmax: 0.004-fold increase | [63] |
Erlotinib | Cyclodextrins | In vivo: rats | Tmax: 5.4-fold decrease Cmax: 3.2-fold increase AUC: 3.6-fold increase | [59] |
Drug (s) | Model | Results | Ref. |
---|---|---|---|
Lumefantrine | In situ: single pass intestinal permeability study | Cellular uptake: 3-fold increase Ka: 2.96-fold increase | [92] |
In vivo: rat intestine | AUC and Cmax: 2.7-fold increase Tmax: no change | ||
Curcumin | In vivo: rat intestine | Lymphatic uptake: 6.3-fold increase Oral bioavailability: 9.5-fold increase Cmax: several folds increase Tmax: 2-fold increase AUC: increased | [90] |
Asenapine maleate | In vitro: Caco-2 cell | Papp: increased | |
In vivo: rat intestine | Bioavailability: 50.19-fold increase AUC: increased Cmax: 20.78-fold increase Tmax: 8-fold increase | [94] | |
4-(N)-docosahexaenoyl 2′, 2′-difluorodeoxycytidine (DHA-dFdC) | In vitro: simulated gastrointestinal fluids | Cmax: increased Tmax: decreased AUC: increased | [95] |
Insulin | Ex vivo: rat everted intestinal sac | Papp: 2-fold increase Cmax: increased AUC: increased | [93] |
Drug (s) | Model | Results | Ref. |
---|---|---|---|
Paeonol | In situ: single-pass intestine perfusion | Papp: 1.64-fold increase Ka: 0.65-fold increase | [115] |
In vitro: everted gut sacs | Papp: increased (p < 0.01) | ||
In vitro: Caco-2 cell | Papp: increased | ||
In vivo: rat intestinal uptake | AUC0→t: 4.27-fold increase Cmax: 4.02-fold increase Tmax: 40-min increase | ||
Berberine hydrochloride | In vivo: rat intestinal uptake | AUC: 4.4-fold increase Cmax: 1.6-fold increase Tmax: 4.3-fold increase | [114] |
In vitro: Caco-2 cell | Papp: increased to 0.574 ± 0.18 × 10−8 cm/s | ||
Curcumin | In vitro: Caco-2 cell | The digested nanoemulsion had the highest permeation rate (7.07 × 105 cm/s) | [109] |
Candesartan cilexetil | In situ single-pass intestinal perfusion | Cellular uptake: 1.75-, 1.93-, and 1.84-fold increase in the duodenum, jejunum, and ileum, respectively. | [111] |
In vitro: Caco-2 cell | The cellular uptake of CCN at 4 °C reduced 92% compared with that at 37 °C (p < 0.01) | ||
In vivo: rat intestinal uptake | AUC: 10-fold increase Cmax: 27-fold increase Tmax: no change | ||
Ibuprofen | In vitro diffusion chamber: rat intestinal membrane | Papp: 10.6-fold | [110] |
In vivo: rat intestinal uptake | AUC 0–6h: 2.2-fold increase Cmax: 27-fold increase Tmax: no change |
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Azman, M.; Sabri, A.H.; Anjani, Q.K.; Mustaffa, M.F.; Hamid, K.A. Intestinal Absorption Study: Challenges and Absorption Enhancement Strategies in Improving Oral Drug Delivery. Pharmaceuticals 2022, 15, 975. https://doi.org/10.3390/ph15080975
Azman M, Sabri AH, Anjani QK, Mustaffa MF, Hamid KA. Intestinal Absorption Study: Challenges and Absorption Enhancement Strategies in Improving Oral Drug Delivery. Pharmaceuticals. 2022; 15(8):975. https://doi.org/10.3390/ph15080975
Chicago/Turabian StyleAzman, Maisarah, Akmal H. Sabri, Qonita Kurnia Anjani, Mohd Faiz Mustaffa, and Khuriah Abdul Hamid. 2022. "Intestinal Absorption Study: Challenges and Absorption Enhancement Strategies in Improving Oral Drug Delivery" Pharmaceuticals 15, no. 8: 975. https://doi.org/10.3390/ph15080975
APA StyleAzman, M., Sabri, A. H., Anjani, Q. K., Mustaffa, M. F., & Hamid, K. A. (2022). Intestinal Absorption Study: Challenges and Absorption Enhancement Strategies in Improving Oral Drug Delivery. Pharmaceuticals, 15(8), 975. https://doi.org/10.3390/ph15080975