Self-Nanoemulsification of Healthy Oils to Enhance the Solubility of Lipophilic Drugs

Podsumowanie

Oils used for drug delivery applications can disrupt the lipid profile of patients, which is undesirable in cardiovascular diseases. Omega-3 fatty acids-rich oils are a healthy alternative to conventional oils and have enormous potential for self-emulsified drug delivery systems.

Streszczenie

The low aqueous solubility of many drugs reduces their bioavailability in the blood. Oils have been used for centuries to enhance the solubility of drugs; however, they can disturb the lipid profile of the patients. In this study, self-nanoemulsifying drug delivery systems of omega-3 fatty acids-rich oils are prepared and optimized for the delivery of lipophilic drugs. Rosuvastatin, a potent hypolipidemic drug, was used as a model lipophilic drug. Fish oil showed more than 7-fold higher solubility of rosuvastatin than other oils and therefore it was selected for the development of self-nanoemulsifying drug delivery systems (SNEDDS). Different combinations of surfactants and co-surfactants were screened and a surfactant mixture of Tween 80 (surfactant) and Capryol PGMC (cosurfactant) were selected for compatibility with fish oil and rosuvastatin. A pseudoternary phase diagram of oil, surfactant, and co-surfactant was designed to identify the emulsion region. The pseudoternary phase diagram predicted a 1:3 oil and surfactant mixture as the most stable ratio for the emulsion system. Then, a response-surface methodology (Box-Behnken design) was applied to calculate the optimal composition. After 17 runs, fish oil, Tween 80, and Capryol PGMC in proportions of 0.399, 0.67, and 0.17, respectively, were selected as the optimized formulation. The self-nanoemulsifying drug delivery systems showed excellent emulsification potential, robustness, stability, and drug release characteristics. In the drug release studies, SNEDDS released 100% of the payload in around 6 h whereas, release of the plain drug was less than 70% even after 12 h. Therefore, omega-3 fatty acids-rich healthy lipids have enormous potential to enhance the solubility of lipophilic drugs whereas, self-emulsification can be used as a simple and feasible approach to exploit this potential.

Wprowadzenie

Lipids have been used for centuries to increase gastrointestinal absorption of water insoluble components of food and medicines¹. Emulsions are the formulations used most widely for oral, intravenous (nutritional supplementation), and topical use². A variety of lipids (fats and oils) are used in the manufacturing of pharmaceutical emulsions and lipid-based self-nanoemulsifying drug delivery systems (SNEDDS). Self-emulsification techniques are widely adopted in pharmaceutical sciences for transmucosal drug delivery. Unlike emulsions, SNEDDS consist of an oil and a surfactant mixture that self-emulsifies in an aqueous medi....

Protokół

1. Screening of the oils, surfactants, and cosurfactants

1. Screening of the oils, surfactants, and co-surfactants for drug solubility
   1. Mix 100 mg of rosuvastatin separately in 1 mL of different omega-3 fatty acids-rich oils (fish oil, olive oil, sesame oil, and linseed oil) and 1 mL of surfactants and cosurfactants (Tween 80, Capryol PGMC, PEG 400, and ethanol) by vortexing for 5 min at a fixed-speed of 2,500 rpm. Then, place in a shaking water bath for 48 h at 50 °C.
   2. After shaking, let the mixture settle for at least 6 h at room temperature so that the undissolved drug is precipitated. Take 0.1 mL of supernatant b....

Wyniki

Herein, nanoformulation of omega-3 fatty acids-rich fish oil are prepared and optimized by self-emulsification with different surfactants and co-surfactants. Figure 1 shows the solubility of rosuvastatin in different oils, surfactants, and co-surfactants. Based on solubility, fish oil was selected as the oil, Tween 80 as the surfactant, and Capryol PGMC as the co-surfactant in the following studies. Table 1 shows the screening of Smix at different ratios to emulsify fish oil.......

Dyskusje

This study was designed to explore the potential of omega-3 fatty acids-rich oil, such as fish oil, sesame oil, olive oil, and linseed oil to act as drug carriers. Self-nanoemulsification was selected as a preferred technique for fabricating the delivery system that lacks water, making it more stable than classical emulsion systems³². Omega-3 fatty acids-rich oils are known for their beneficial health effects¹⁸. They have been used as a supplement for various diseases such .......

Materiały

Name	Company	Catalog Number	Comments
Ammonium acetate	Sigma-Aldrich, Germany	A1542	Analytical grade
Capryol PGMC	Gattefossé, France	RT9P9S09QI	Analytical grade
Design Expert Software	StatEase, United States	Version 12.0.3.0	Analytical software (freely available for subscription)
Dialysis tubing (12,000 Daltons MWCO)	Visking, UK	12000.02.30	Pure regenerated natural cellulose membranes with 12,000 Daltons MWCO
Dissolution apparatus	Memmert, Germany	SV 1422	USP type II dissolution apparatus
Ethanol	Honeywell, Germany	24194	Analytical grade
Fish oil	Wilshire Labs Pvt(Ltd), Pakistan	not applicable	Received as gift sample.
Hydrochloric acid	BDH Laboratories Ltd, UK	BDH3036-54L	Analytical grade
Methanol	Honeywell, Germany	34966	Analytical grade
Refrigerator (Pharmaceutical)	Panasonic, Pakistan	MPR-161 DH-PE	Refrigerator for storage at 4 °C
Rosuvastatin calcium	Searle Pharmaceuticals Pvt(Ltd) Pakistan	not applicable	Received as gift sample.
Sodium Hydroxide	Honeywell, Germany	38215	Analytical grade
Span 80	BDH Laboratories Ltd, UK	MFCD00082107	Analytical grade
Triplot Software	MS Excel spreadsheet developed by Tod Thompson	Triplot Ver. 4.1.2	Analytical software (freely available)
Tween-80	Sigma-Aldrich, Germany	P1754-500ML	Analytical grade
UV-Vis spectrophotometer	Dynamica, UK	Halo DB-20	Double beam spectrophotometer
Water Bath	Memmert, Germany	WNB 7	Water batch for heating up to 70 °C