Cetomacrogol - an overview | ScienceDirect Topics (2023)

Characterization of polyoxyethylene alkyl ethers

Brij-58 (also known as polyoxyl 20 cetyl ether) and Brij S-100 (also known as polyoxyl 100 stearyl ether) are polyoxyethylene alkyl ether nonionic surfactants. They are used in pharmaceuticals as emulsifying agents, gelling/foaming agents, to increase the drug release of suppository formulations or to provide hydrophilicity to polymeric nanoparticles [76]. Analysis of this class of excipient has previously been undertaken using capillary electrophoresis hyphenated to mass spectrometry [87]. SFC was explored for this class of compounds by Lafosse et al. [84] who analyzed the BC 7 ethoxylated surfactant oligomer using ELS detection with a silica stationary phase and a carbon dioxide mobile phase modified with a mixture of methanol, water and triethylamine.

Creams

These are emulsions of either oil in water (washable; cosmetic ‘vanishing’ creams) or water in oil. The water content allows the cream to rub in well. A cooling effect (cold creams) is obtained with both groups as the water evaporates.

Basic Chemistry

6.3 Solution-phase stability

Ren et al. [75] investigated the chemical stability of a rabeprazole sodium, which was evaluated in a simulated intestinal fluid (pH 6.8) containing various “Generally Recognized As Safe (GRAS)”-listed excipients, including Brij® 58, Poloxamer 188, Cremophor RH40, Gelucire 44/14 and PEG 6000. The quantities of rabeprazole and the thioether-rabeprazole product were quantified by HPLC after incubation at 37 and 60°C. The major degradation component was isolated and characterized by LC/MS. Rabeprazole degradation followed kinetics of the first order. The rate constants (k) obtained at 37 and 60°C was 0.75 and 2.78h⁻¹, respectively. By comparison, its stability was enhanced by incorporating excipients. Brij®58 had the greatest stabilizing effect of several excipients tested in this experiment. At 37 and 60°C, for instance, the k values of Brij®58 decreased to 0.22 and 0.53h⁻¹. In terms of their solubilizing performance and micellar formulation of thioether rabeprazole, the stability mechanisms of these hydrophilic polymer was excellent devices with optimum Hydrophile-lipophile balance (HLB) values explained in detail. In addition, formulations containing sufficient excipients of rabeprazole would improve the stability and bioavailability of the intestinal tract.

Charge inducers

Electrostatic stabilization of the niosomes can strongly suppress their aggregation. It can be achieved by inclusion of charge inducers such as dicetyl phosphate, stearylamine and diacylglycerol [104]. The presence of charged groups or inert and bulky surface groups on the niosome surface (by attaching polyelectrolytes, polysaccharides, etc. on the surface) enhances steric repulsion, which leads to improved stability [102].

Pardakhty et al. prepared niosomes of polyoxyethylene alkyl ethers (Brij) for encapsulation of insulin by a film hydration method. Brij 35 and Brij 58 did not form niosomes in the absence of cholesterol, apparently because of relatively large polar head groups in comparison with their alkyl chains. The size of vesicles was found to be dependent on the cholesterol content, charge incorporation or hydrophilicity of surfactants [105]. Encapsulation of insulin in the closed bilayer structure of niosomes protected it against degradation by gastric and intestinal enzymes. The maximum proteolytic activity was found in Brij 92/cholesterol (7:3 molar ratios), in which only 26.3 ± 3.98% of entrapped insulin was released during 24h in simulated intestinal fluid (SIF). The drug release kinetics for formulations could be best explained by the Baker and Lonsdale equation, indicating a diffusion-based delivery mechanism. The above results indicated that niosomes could be formulated as a sustained release oral carrier for the delivery of peptides/proteins such as insulin [105].

Encapsulation of human insulin in lipid vesicular systems such as niosomes was sought as a route to protect this protein against proteolytic enzymes and to improve its oral bioavailability. Recombinant human insulin was entrapped in multilamellar niosomes composed of polyoxyethylene alkyl ether surfactants (Brij 52 and Brij 92) or sorbitan monostearate (Span 60) and cholesterol. The extent and rate of insulin release from Brij 92 and Span 60 vesicles were lower than from Brij 52 niosomes (p < 0.05). Vesicles significantly protected insulin against proteolytic enzymes in comparison with free insulin solution (p < 0.05). Animals treated with oral niosome-encapsulated insulin (100IU/kg) showed decreased levels of blood glucose and elevated serum insulin; in the case of Brij 92 niosomes, the hypoglycaemic effect was significant (p < 0.05).

Niosomes were also stable in solubilizing bile salt solutions and could effectively prolong the release of insulin in both simulated gastric fluid and intestinal fluid (SGF and SIF). Results of this study showed that niosomes may be utilized as oral carriers of insulin; however, to increase bioavailability of insulin, further studies on protease inhibitor co-encapsulation in niosomal formulations might be helpful [106].

Niosomes of sorbitan monoesters (Span 20, 40, 60 and 80) were prepared by the film hydration method without sonication. Span 80 did not form niosomes in the absence of cholesterol. Depending on the cholesterol molar ratio or charge incorporation, the size of vesicles varied. The amount of insulin released in SIF from Span 20 and 80 was higher than from Span 40 and 60 vesicles. Span 60 vesicles showed the highest protection of insulin against gastric and intestinal enzymes and also exhibited good stability in the presence of sodium deoxycholate and storage temperatures [107].

Both hydrophilic and hydrophobic substances can be embedded in niosomal vesicles. The encapsulation of pharmaceutical materials in niosomes can decrease toxicity of the drug, enhance drug absorption, stability or activity, and slow down removal of the drug from the circulation due to slow drug release [94].

In short, studies suggest that niosomes are able to stabilize insulin against enzymatic degradation, and they may be potential candidates as oral carriers of this protein.

2.1 Introduction

As is well known, surfactants show interesting interfacial and bulk properties (Geetha and Tyagi, 2012) and have a wide variety of uses (Paul and Moulik, 2001). If one excludes other potential purposes, surfactants are one of the most exploited raw materials in the formulation of versatile cosmetic products, but also one of the most important classes of pharmaceutical excipients, finding a wide range of uses in pharmaceutical preparations. Depending on the type of formulation, surfactants may play a role in solubilization or stabilization of cosmetic actives/drugs in different liquid preparations, improve physical stability and textural characteristics of emulsion systems and semisolids, or alter the flow properties of powders and granulates in the manufacturing of solid cosmetics or pharmaceutical dosage forms (Corrigan and Healy, 2002). Moreover, surfactants play an important role in the development of colloidal delivery systems for cosmetics and active pharmaceutical ingredients (APIs), such as reverse micelles, vesicles, liquid crystal dispersions, nanoemulsions and nanoparticles (Müller-Goymann, 2004).

In addition, surfactants strongly affect biological membranes, changing their permeability and thus, for instance, influencing the penetration of drugs and cosmetic actives into the skin. This behaviour is strongly related to surfactants’ safety profiles, as they also have the capacity to irritate the skin and damage biological membranes (Savic et al., 2010). Although this phenomenon is mainly concentration-dependent, it is particularly related to the so-called traditional/conventional surfactants/emulsifiers. For example, if one considers the field of dosage forms/drug delivery systems design, though a large number of commercial surfactants are available, a proportionally small group of them are approved as pharmaceutical excipients, and therefore widely accepted by the pharmaceutical industry. From this group, surfactants of particular pharmaceutical importance include anionic sodium lauryl sulphate (SLS/SDS) and non-ionic polyoxyethylated glycol monoethers (e.g. cetomacrogol), sorbitan esters (Span®) and ethoxylated sorbitan esters or polysorbates (Tween®) (DAB 2006; BP 2009; Ph. Eur. 7; USP/NF 35). In fact, it could be said that a whole series of potential uses of surfactants could be perfectly covered by the conventional representatives.

However, increased attention given to the environment over the past few decades has produced a growing interest in the field of the so-called natural surfactants. This term relates, in its broadest sense, to surface-active substances coming from natural raw materials. Generally, there are three categories of natural surfactants: amphiphiles produced by yeast or bacteria, amphiphiles containing a natural polar headgroup, and amphiphiles containing a natural hydrophobic tail. Sugars and amino acids are the two most important examples of surfactant polar headgroups of natural origin (Holmberg, 2001; Johansson and Svensson, 2001;Stubenrauch, 2001). As well as the awareness of environmental protection, there is an increase in demand for natural products, already elaborated in the previous chapter. Still, the range of surfactants suitable for the formulation of authentic natural cosmetics is quite limited (Alkyl Glucosides, Alkyl Glutamates, Alkyl Citrates, Alkyl Lactylates, Alkyl Sulphates, Alkyl Tartrates, protein derivatives, soaps, natural betaines or saponins), according to the standards of non-governmental organizations (NGOs) such as NaTrue (The International Natural and Organic Cosmetic Association), BDIH (Bundersverband der Industrie- und Handelsunternehmen) and COSMOS (cosmetic organic and natural standard). To be part of a natural cosmetic product, all ingredients (including surfactants) should be evaluated not only with respect to their origin, but also taking into account other criteria, such as the applied manufacturing process, by-products, preservation systems, biological degradation and aquatic toxicity (Hauthal, 2012). Although there are certain surfactants that are accepted by all the organizations mentioned, there are still some differences regarding their acceptance criteria. From the aforementioned it is clear that Alkyl Polyglucosides (APGs), also known as Alkyl Glucosides, could be safely used as primary/basic surfactants as well as co-surfactants in the formulation of those cosmetic products declared as natural. Indeed, APGs are commonly defined as a newer class of so-called natural, polyethylene glycol (PEG)-free surfactants, produced from renewable resources (von Rybinski and Hill, 1998;Holmberg, 2001; Stubenrauch, 2001; Tasic-Kostov et al., 2011a). In this vein, their biodegradability, accompanied by their natural origin, means they could be considered as the most important sugar-based surfactants today (Tasic-Kostov et al., 2011a). There is a strong interest in exploring APGs as surfactants for several types of application, since they are multifunctional substances that have proved to be very efficient in different cleaning products. There are also certain indications that some of them could be used as food emulsifiers (Tasic-Kostov et al., 2011a).

On the other hand, APGs were studied as prospective surfactants/emulsifiers for emulsion systems stabilized with lamellar phases of liquid crystalline (Lα) and/or gel crystalline (Lβ) type with high potential for skin moisturization, which could be a useful property for both cosmetic and pharmaceutical products (Savic et al., 2004; Savic et al., 2005a; Savic et al., 2005b; Savic et al., 2006; Savic et al., 2007; Savic et al., 2008a; Savic et al., 2008b; Savic et al., 2009a; Savic et al., 2009b; Savic et al., 2010; Tasic-Kostov et al., 2010; Kovacevic et al., 2011; Savic et al., 2011; Tasic-Kostov et al., 2011a; Tasic-Kostov et al., 2011b; Jaksic et al., 2012; Tasic-Kostov et al., 2012; Lukic et al., 2013). Therefore, APGs will be the focus of this chapter as structure-dependent promoters of lamellar mesophases. The chapter will provide crucial information on their physicochemical characteristics as well.

3 Results