Novel Drug Delivery Approach via Self-Microemulsifying Drug Delivery System for Enhancing Oral Bioavailability of Asenapine Maleate: Optimization, Characterization, Cell Uptake, and In Vivo Pharmacokinetic Studies

Patel, Manthan; Mundada, Veenu P; Sawant, Krutika

doi:10.1208/s12249-018-1212-z

Cited by 34 publications

(12 citation statements)

References 33 publications

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“…The capsule containing SNEDDS equivalent to 16 mg of Candesartan was incorporated into the buffer media after initiating rotation of the paddle. Aliquots (5 ml) were withdrawn after 30 min and analyzed by UV spectroscopy at kmax 254 nm (Patel et al, 2019). The experiment was repeated in triplicates.…”

Section: Design Of Experiments (Doe) To Optimize Sneddsmentioning

confidence: 99%

Design and optimization of candesartan loaded self-nanoemulsifying drug delivery system for improving its dissolution rate and pharmacodynamic potential

Verma

Kaushik

2020

Drug Delivery

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During the last decades, much attention has been focused on SNEDDS approach to resolve concerns of BCS II class drugs with accentuation on upgrading the solubility and bioavailability. The present hypothesis confirms the theory that SNEDDS can reduce the impact of food on Candesartan solubilization, thereby offering the potential for improved oral delivery without co-administration with meals. The present studies describe quality-by-design-based development and characterization of Candesartan loaded SNEDDS for improving its pharmacodynamic potential. D-optimal mixture design was used for systematic optimization of SNEDDS, which showed globule size of 13.91 nm, more rapid drug release rate of >90% in 30 min and 16 s for self-emulsification. The optimized formulations were extensively evaluated, where an in vitro drug release study indicated up to 1.99-and 1.10-fold enhancement in dissolution rate from SNEDDS over pure drug and marketed tablet. In vivo pharmacodynamic investigation also showed superior antihypertensive potential of SNEDDS in normalizing serum lipid levels as compared to pure drug and marketed tablet that was executed on male Wistar rats. Overall, this paper reports successful systematic development of candesartan-loaded SNEDDS with distinctly improved biopharmaceutical performance. This research work interpreted a major role of SNEDDS for enhancing the rate of dissolution and bioavailability of poorly water soluble drugs.

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Section: Design Of Experiments (Doe) To Optimize Sneddsmentioning

confidence: 99%

Design and optimization of candesartan loaded self-nanoemulsifying drug delivery system for improving its dissolution rate and pharmacodynamic potential

Verma

Kaushik

2020

Drug Delivery

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“…As Transcutol P has shorter chain length (C6), it is considered more efficient and can easily promote water penetration at interface. [23] In general, the longer the length of the hydrophobic alkyl chain, the higher the molecular volume of the oil phase affecting the emulsification ability of surfactant mixtures. In this view, cinnamon oil is a C9 medium chain fatty acid that can be easily emulsified.…”

Section: Dissolution Studiesmentioning

confidence: 99%

Untitled

Desavathu¹

2020

AJP

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Aim: The objective of this study was to develop a novel self-nanoemulsifying drug delivery system which produced very small and uniform emulsion droplets, resulting in enhanced solubility, dissolution, and oral bioavailability of poorly water-soluble rosuvastatin calcium. Material and Methods: The effects of oil, surfactant, and cosurfactant on the drug solubility were assessed, and pseudoternary phase diagrams were plotted. Among the liquid SNEDDS formulations tested, the liquid SNEDDS composed of cinnamon oil (oil), Cremophor RH 40 (surfactant), and Transcutol P (cosurfactant) at a ratio of 1:5 (o/S mix), produced the smallest emulsion droplet size. The rosuvastatinloaded liquid SNEDDS formulation was assessed for the emulsion droplet size, solubility, and dissolution of the emulsified SNEDDS and compared to the pure drug. Different SNEDDS formulations of rosuvastatin calcium were prepared by aqueous phase titration method. Prepared SNEDDS was filled in capsule shells as drugs with high solubility or low dose can be filled in capsule shell. Prepared SNEDDS was subjected to different thermodynamic stability tests. Thermodynamically stable SNEDDS was selected for self-nanoemulsification efficiency test. Selected formulations were characterized in terms of droplet size distribution, viscosity. Finally, selected SNEDDS (F1-F8) was subjected to in vitro dissolution/drug release studies. Results and Discussion: Droplet size and viscosity of formulation F6 were found to be lowest as compared to other formulations. The results of zeta potential indicated the formation of stable SNEDDS. In vitro drug release studies showed 97.7% release of drug from optimized formulation F6, where initial drug release profile of rosuvastatin calcium from optimized formulation F6 was found to be much faster than marketed rosuvastatin calcium capsule. Conclusion: Thus, this novel SNEDDS developed represents a potentially powerful oral delivery system for rosuvastatin calcium to enhance solubility and thereby bioavailability.

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“…It is an isotropic mixture of oil, emulsifiers, co-emulsifiers, and the drug substance. SMEDDS can increase the oral bioavailability of compounds [13][14][15], regulate hydrophobicity surfaces [16,17], and promote the uptake and transport of compounds [18,19]. SMEDDS can rapidly form nanoscale emulsion droplets spontaneously in an aqueous medium [20], such as water or gastrointestinal fluid, and encapsulate the active pharmaceutical ingredient (API) present in the medium [13].…”

Section: Introductionmentioning

confidence: 99%

Improved Safety and Anti-Glioblastoma Efficacy of CAT3-Encapsulated SMEDDS through Metabolism Modification

Wang

et al. 2021

Molecules

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13a-(S)-3-pivaloyloxyl-6,7-dimethoxyphenanthro(9,10-b)-indolizidine (CAT3) is a novel oral anti-glioma pro-drug with a potent anti-tumor effect against temozolomide-resistant glioma. 13a(S)-3-hydroxyl-6,7-dimethoxyphenanthro(9,10-b)-indolizidine (PF403) is the active in vivo lipase degradation metabolite of CAT3. Both CAT3 and PF403 can penetrate the blood–brain barrier to cause an anti-glioma effect. However, PF403, which is produced in the gastrointestinal tract and plasma, causes significant gastrointestinal side effects, limiting the clinical application of CAT3. The objective of this paper was to propose a metabolism modification for CAT3 using a self-microemulsifying drug delivery system (SMEDDS), in order to reduce the generation of PF403 in the gastrointestinal tract and plasma, as well as increase the bioavailability of CAT3 in vivo and the amount of anti-tumor substances in the brain. Thus, a CAT3-loaded self-microemulsifying drug delivery system (CAT3-SMEDDS) was prepared, and its physicochemical characterization was systematically carried out. Next, the pharmacokinetic parameters of CAT3 and its metabolite in the rats’ plasma and brain were measured. Furthermore, the in vivo anti-glioma effects and safety of CAT3-SMEDDS were evaluated. Finally, Caco-2 cell uptake, MDCK monolayer cellular transfer, and the intestinal lymphatic transport mechanisms of SMEDDS were investigated in vitro and in vivo. Results show that CAT3-SMEDDS was able to form nanoemulsion droplets in artificial gastrointestinal fluid within 1 min, displaying an ideal particle size (15–30 nm), positive charge (5–9 mV), and controlled release behavior. CAT3-SMEDDS increased the membrane permeability of CAT3 by 3.9-fold and promoted intestinal lymphatic transport. Hence, the bioavailability of CAT3 was increased 79% and the level of its metabolite, PF403, was decreased to 49%. Moreover, the concentrations of CAT3 and PF403 were increased 2–6-fold and 1.3–7.2-fold, respectively, in the brain. Therefore, the anti-glioma effect in the orthotopic models was improved with CAT3-SMEDDS compared with CAT3 in 21 days. Additionally, CAT3-SMEDDS reduced the gastrointestinal side effects of CAT3, such as severe diarrhea, necrosis, and edema, and observed less inflammatory cell infiltration in the gastrointestinal tract, compared with the bare CAT3. Our work reveals that, through the metabolism modification effect, SMEDDS can improve the bioavailability of CAT3 and reduce the generation of PF403 in the gastrointestinal tract and plasma. Therefore, it has the potential to increase the anti-glioma effect and reduce the gastrointestinal side effects of CAT3 simultaneously.

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Novel Drug Delivery Approach via Self-Microemulsifying Drug Delivery System for Enhancing Oral Bioavailability of Asenapine Maleate: Optimization, Characterization, Cell Uptake, and In Vivo Pharmacokinetic Studies

Cited by 34 publications

References 33 publications

Design and optimization of candesartan loaded self-nanoemulsifying drug delivery system for improving its dissolution rate and pharmacodynamic potential

Design and optimization of candesartan loaded self-nanoemulsifying drug delivery system for improving its dissolution rate and pharmacodynamic potential

Untitled

Improved Safety and Anti-Glioblastoma Efficacy of CAT3-Encapsulated SMEDDS through Metabolism Modification

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