Research paper
Octacosanol educes physico-chemical attributes, release and bioavailability as modified nanocrystals

https://doi.org/10.1016/j.ejpb.2017.06.020Get rights and content

Abstract

Octacosanol is a lesser known nutraceutical with the potential for treatment of several inflammatory diseases, high cholesterol, Parkinson’s symptoms and tumour growth along with the capacity to improve athletic performance. But its lipophilicity and large structure inhibits extended solubility in water resulting in poor absorption and a low bioavailability. In the present work, sodium salt of octacosyl sulfate was synthesized. It displayed improved water solubility. Its nanocrystals, synthesized by means of nanoprecipitation technique, enhanced diffusion velocity, antioxidant capacity, shelf-life, penetrability and bioavailability. Particle size of the nanocrystals ranged between 197 and 220 nm. Both modified octacosanol and its nanocrystals displayed maximum lipid peroxidation activities at a concentration 1000 ppm, but nanocrystals demonstrated higher prevention. From freeze-thaw cycles it was evident that normal octacosanol crystals were far more prone to temperature variations than the nanocrystals. A pronounced increase in release/diffusion rate and bioavailability was observed for the nanocrystals of the modified octacosanol. In vitro release kinetics, bioavailability and bioequivalence were studied. Relative bioavailability for gastric passage and pancreatic passage of nanocrystals was 2.58 times and 1.81 times that of normal crystals respectively. Furthermore the nanocrystals displayed a superior in vitro release rate, while following a non-Fickian mode.

Introduction

Octacosanol is a long 28 carbon aliphatic hydrocarbon chain culminating in a hydroxyl group. Rice bran is an unexploited source of octacosanol. Octacosanol has many constructive effects on health, including anti-bacterial activities, cholesterol lowering properties, cell protective effects and most recently anti-Parkinsonism [1], [2], [3]. However as the name implies (“fatty” alcohol), it is hydrophobic in nature which limits its application considerably due to its minimal solubility. It is insoluble in water and only marginally soluble in edible oils at room temperature. This meagre solubility minimizes the uptake of octacosanol thus delaying its health promoting effects. Many formulation approaches can be adopted for enhancing the solubility of octacosanol. They include complexation using cyclodextrin, synthesis of gelatine capsules containing oil-based compounds or nanoencapsulation of these low soluble products by developing emulsions with them [4], [5], [6]. However improving the solubility of octacosanol does not solely entail its sufficient bioavailability. Bioavailability basically measures the active proportion of a compound which is absorbed within a system [7]. By modifying the morphology of a compound, its functional traits can be altered, thus enhancing its bioavailability. This situation can be targeted by means of developing nanocrystals of octacosanol in its soluble form. The adjuvant effect of nanocrystals promotes large surface-to-volume ratios which foster radical transformation and subsume desired features into a compound [8]. Generally mucosal/oral administration of any drug or nutraceutical is desirable as this technique activates the immune system of the body and contributes towards the competence of the compound [9].

Nanocrystallization is such an approach which ascertains the self-modification of a particular compound to boost its penetrability due to the diminutive size and directed delivery. This technique can be applied to any compound without the involvement of any cumbersome procedure. Nanocrystallization has been applied on low soluble drugs till date [6], [10]. However nutraceuticals like octacosanol have yet not been nano-fabricated, though there is immense potential to improve their activities by nano-formulating them. Some works on the nanoencapsulation of oil-soluble nutraceuticals have been done so far [11], [12], [13]. But conventional nanocrystallisation is far more advantageous than nanoencapsulation, as the nanocrystals are composed of 100% of the active unit, at the same time being independent of any other carrier materials as necessary for nanocapsules [14]. Furthermore decreasing size of the compound leads to an increase in the surface area resulting in the enhancement of dissolution velocity. Thus it is expected that a higher bioavailability will be obtained [14].

In the present work octacosanol was converted to its soluble form by sulfation followed by converting it to its sodium salt. This was then precipitated as nanocrystals by solvent displacement method. Physico-chemical characteristics of both nanocrystals and normal octacosanol sulfate crystals were determined. Thereafter the behaviour of both these products on an in vitro gastro-intestinal simulated model was studied. The primary objective of the present study was to analyse the difference between the rate of absorption of normal sodium octacosanol sulfate crystals and its nano-formulations. The passage of a compound across a biological membrane is pivotal in determining its efficacy as a nutraceutical and hence the entire release/diffusion study was performed using dialysis tubings (a mimic of the biological membrane) on an in vitro gastro-intestinal model.

Section snippets

Materials

Wax, obtained from refining of rice bran oil, was collected from Sethia Oils Limited, West Bengal, India. The wax was then de-oiled with acetone, dried and finally weighed to be about 100 g. Octacosanol was isolated and purified from the wax following the method of Pollard et al. [15], after a few minor modifications. Isolated compound was confirmed by GC–MS analysis against standard octacosanol procured from Sigma-Aldrich Co., St. Louis, USA. The amount of octacosanol collected was 20 g. All

Morphology observation

Fig. 1A and B portray the SEM micrographs of sodium octacosyl sulfate (SOS) and Fig. 1C and D that of sodium octacosyl sulfate nanocrystals (SOSN) respectively. Fig. 1C and D shows the morphological evolution of SOS as the compound (Fig. 1A and B) is nanocrystallised. The general particle size of the dried octacosyl sulfate before conversion to nanoparticles is observed to be 536.58 nm (Fig. 1A and B). However in case of SOSN, the particle-size ranges between 197 and 220 nm (Fig. 1C and D). In Fig. 1

Conclusion

From the studies it is evident that development of nanocrystals of 1-octacosyl sulfate sodium salt considerably enhanced the bioavailability of the fatty alcohol. The primary objective for development of any nutraceutical delivery system is to ensure its maximum efficacy. To establish this, the release and bioavailability study in a particular dosage formulation is of utmost importance. At this juncture the mathematical models play an important role in the elucidation of the release behaviour

Conflict of interest

The authors have declared no conflict of interest.

Acknowledgement

The authors would like to acknowledge the ‘Council of Scientific and Industrial Research’ (CSIR), India for their financial support. Furthermore the Centre for Research in Nanoscience and Nanotechnology (CRNN), University of Calcutta, West Bengal, India is acknowledged for extending their SEM facilities.

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