W. P. Oliveira, V.C. Pessan, V.A. Secolin and C.R.F. Souza*

Faculty of Pharmaceutical Sciences of Ribeirão Preto/USP, Ribeirão Preto, SP, Brazil

Figure 2. Lipid compositions developed: (a) with cholesterol and (b) with stearic acid.

( A ) ( B )

Figure 5. Optical microscopy of compositions

containing cholesterol (50 and 500 x).

Figure 6. Optical microscopy of compositions

containing stearic acid (50 and 500 x).

Figure 4. Visual aspect of spray dried lipid dispersions

obtained with cholesterol (A) and stearic acid (B) with

membrane stabilizer.

( A ) ( B )

INTRODUCTION

OBJECTIVES

Recently, advances in pharmaceutical research is focused on new delivery

systems utilizing new devices to achieve modification of delivery time, targeting, as

well as improve the in vivo solubility and hence bioavailability of poorly soluble

drugs. Liposomes consist of one or more lipid and/or phospholipid bilayers can

contain other molecules such as proteins or carbohydrates in their structure and

are generally classified by their structural properties or by the method of

preparation of the vesicles (MOZAFARI et al, 2008). Have as main advantage the

ability to encapsulate water soluble active (inside the cavity) and soluble (in the

bilayer) (Figure 1a). However, liposomal systems have the disadvantage of low

stability due to its high water content limiting their long-term storage (shelf life).

Payne et al. (1986) proposed the production of stable liposomes, by obtaining pro-

liposomes, which are dried product with good flow properties, the active

compounds and phospholipids which, upon addition of water disperse to form a

multi-lamellar liposome (Figure 1b).

Figure 1. (a) encapsulation of water-soluble and fat-soluble bioactive in liposomal systems, and (b)

formation of multi-lamellar liposome of proliposome by addition of water and stirring controlled.

The aim of this work was the development and characterization of

proliposomes loaded with lyophilized extract of P. guajava through spray drying. It

was evaluated the effects of the stabilizer of the lipid membrane (CH: cholesterol or

AS: stearic acid), and the drying and stabilizer agents (GL: glycerol, SB: sorbitol,

TR: trehalose and LC: lactose).

MATERIAL AND METHODS

Development of lipid compositions loaded with P. guajava bioactive

compounds: hydrogenated soy phosphatidylcholine 90 % (Phospholipon® 90H,

Lipoid GMBH), and cholesterol 94 % (Sigma-Aldrich) or stearic acid (Via pharma,

Brazil) as lipid membrane stabilizer were used. Four carbohydrates, namely,

glycerol (BASF), sorbitol (Sigma-Aldrich), lactose M-200 (Natural Pharma Ltda,

Brazil) and D(+) trehalose (Sigma-Aldrich) were evaluated as drying and stabilizer

agent of the lipid system. The lipid dispersions were prepared according Secolin et

al. (2014), using 4 % of soy lecithin, 2 % of lyophilized extract, 12 mL of n-butyl

alcohol as lipids solubilizer (Table 1).

Table 1: Membrane stabilizer and drying adjuvant added to lipid composition.

Production of proliposomes by spray drying: The stable lecithin based

dispersions were dried in a Lab-Plant SD-05 spray dryer (Lab-Plant Ltd, UK)

(Figure 3). Feed rate of 4 g/min, inlet temperature 100 °C, drying gas flow rate 60

m3/h, pressure and spray gas flow: 5 kgf/cm2 and 17 lpm. The proliposomes were

characterized through determination of the moisture content (Xp), water activity

(aW), total polyphenols (PT), bulk and tapped density (b and t) and flow properties

(Carr´s index - IC) and Hausner ratio - HR) (Table 2).

Figure 3. Spray dryer used.

RESULTS AND DISCUSSION

CONCLUSIONS

REFERENCES

MOZAFARI, M.R. et al., Int. J. Food Properties, 11, 833–844, 2008.

PAYNE, N.I.; et al., J. Pharm. Sci., 75(4):325–329, 1986.

SECOLIN, V.A.; OLIVEIRA W.P.; SOUZA, C.R.F. Anais XXXVI Congresso Brasileiro de Sistemas Particulados, 1-10, 2014.

The formulation LPG4 (CH and LC), showed a better drying performance,

generating a product with Xp values (2.5%) and aW (0.21), and high concentration

of PT (14.2%).

The spray dried proliposomes were classified as cohesive and restrict flow

powders.

Figures 5 and 6 show the obtained optical microscopy, obtained globules sizes

of 5 and 10 microns for formulations containing for cholesterol and stearic acid

respectively; all remained homogeneous and stable (Figure 2). The rheological

analysis showed that all the formulations analyzed exhibit non-Newtonian behavior

of pseudoplastic type.

Table2: Physicochemical characterization of the spray dried proliposomes.

swelling water dried lipid membrane

agitation

Lipid layer

fat-soluble active

in the bilayer

water-soluble active

inside the bilayer