Further characterization of theobroma oil-beeswax admixtures as lipid matrices for improved drug delivery systems.

There is an increasing interest in lipid based drug delivery systems due to factors such as better characterization of lipidic excipients and formulation versatility and the choice of different drug delivery systems. It is important to know the thermal characteristics, crystal habit, texture, and appearance of a new lipid matrix when determining its suitability for use in certain pharmaceutical application. It is line with this that this research was embarked upon to characterize mixtures of beeswax and theobroma oil with a view to applying their admixtures in drug delivery systems such as solid lipid nanoparticles and nanostructured lipid carriers. Admixtures of theobroma oil and beeswax were prepared to contain 25% w/w, 50% w/w, and 75% w/w of theobroma oil. The admixtures were analyzed by differential scanning calorimetry (DSC), small angle X-ray diffraction (SAXD), wide angle X-ray diffraction (WAXD), and isothermal heat conduction microcalorimetry (IMC). The melting behavior and microstructures of the lipid admixtures were monitored by polarized light microscopy (PLM). Transmission electron microscopy (TEM) was used to study the internal structures of the lipid bases. DSC traces indicated that the higher melting peaks were roughly constant for the different admixtures, but lower melting peaks significantly increased (p < 0.05). The admixture containing 25% w/w of theobroma oil possessed highest crystallinity index of 95.6%. WAXD studies indicated different reflections for the different lipid matrices. However, new interferences were detected for all the lipid matrix admixtures between 2theta = 22.0 degrees and 2theta = 25.0 degrees. The lipid matrices containing 50% w/w and 25% w/w of theobroma oil showed absence of the weak reflection characteristic of pure theobroma oil, while there was disappearance of the strong intensity reflection of beeswax in all the lipid matrix admixtures at all stages of the study. PLM micrographs revealed differences with regard to the thermal and optical behaviors depending on the composition of the matrix. The lipid matrix consisting of 75% w/w of theobroma oil showed a spherulite texture after 4 weeks of isothermal storage. Crystallization exotherms of lipid matrices containing 50% w/w and 25% w/w of theobroma oil showed change in modification after 30 min with the latter having a greater time-dependent crystallization. Generally, low non-integral Avrami exponents and growth rate constants were obtained for all the lipid matrices, with the admixture containing 25% w/w theobroma oil having the lowest Avrami exponent and growth rate constant. Based on the results obtained, admixtures containing 50% w/w and 75% w/w of theobroma oil could be applied in the formulation of solid lipid nanoparticles and nanostructured lipid carriers as these lipid matrices possessed crystal characteristics that favour such drug delivery systems.

[1]  Alejandro G. Marangoni,et al.  Relationship between Crystallization Behavior and Structure in Cocoa Butter , 2003 .

[2]  M. Stuchlík,et al.  Lipid-based vehicle for oral drug delivery. , 2001, Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia.

[3]  H. Möhwald,et al.  Small angle X-ray scattering (SAXS) and differential scanning calorimetry (DSC) studies of amide phospholipids. , 2005, Chemistry and physics of lipids.

[4]  S. Miura,et al.  Crystallization behavior of 1,3-dipalmitoyl-2-oleoyl-glycerol and 1-palmitoyl-2,3-dioleoyl-glycerol , 2001 .

[5]  J. Bouwstra,et al.  Structure of human stratum corneum as a function of temperature and hydration a wide-angle X-ray diffraction study , 1992 .

[6]  P. Supaphol Application of the Avrami, Tobin, Malkin, and Urbanovici–Segal macrokinetic models to isothermal crystallization of syndiotactic polypropylene ☆ , 2001 .

[7]  J. A. Solís-Fuentes,et al.  Mango seed uses: thermal behaviour of mango seed almond fat and its mixtures with cocoa butter. , 2004, Bioresource technology.

[8]  T. Nyholm,et al.  A calorimetric study of binary mixtures of dihydrosphingomyelin and sterols, sphingomyelin, or phosphatidylcholine. , 2003, Biophysical journal.

[9]  Hoo-Kyun Choi,et al.  Preparation and characterization of solid lipid nanoparticles (SLN) made of cacao butter and curdlan. , 2005, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[10]  Y. Amemiya,et al.  Thermodynamic and Kinetic Study on Phase Behavior of Binary Mixtures of POP and PPO Forming Molecular Compound Systems , 1997 .

[11]  Casimir C. Akoh,et al.  Structured Lipids-Novel Fats with Medical, Nutraceutical, and Food Applications. , 2002, Comprehensive reviews in food science and food safety.

[12]  M. Buchgraber,et al.  Analytical platforms to assess the authenticity of cocoa butter , 2003 .

[13]  J. Bernal,et al.  Physico‐chemical parameters for the characterization of pure beeswax and detection of adulterations , 2005 .

[14]  J. Fonollosa,et al.  X-ray diffraction analysis of internal wool lipids. , 2004, Chemistry and physics of lipids.

[15]  J. deMan,et al.  Short spacings and polymorphic forms of natural and commercial solid fats: A review , 1990 .

[16]  M. Povey,et al.  Structure and transformation of low-temperature phases of 1,3-distearoyl-2-oleoyl glycerol , 2004 .

[17]  C. Müller-Goymann,et al.  Influence of different ceramides on the structure of in vitro model lipid systems of the stratum corneum lipid matrix. , 2002, Chemistry and Physics of Lipids.

[18]  M. Avrami Kinetics of Phase Change. I General Theory , 1939 .

[19]  X. Kong,et al.  Isothermal crystallization kinetics of PEO in poly(ethylene terephthalate)–poly(ethylene oxide) segmented copolymers. I. Effect of the soft‐block length , 2000 .

[20]  C. Lopez,et al.  Thermal and structural behavior of milk fat. 1. Unstable species of anhydrous milk fat. , 2001, Journal of dairy science.

[21]  Characterization of eutectic mixtures in different natural fat blends by thermal analysis , 2003 .

[22]  W. Siew Crystallisation and melting behaviour of palm kernel oil and related products by differential scanning calorimetry , 2001 .

[23]  K. Roberts,et al.  Identification of the Initial Nucleating Form Involved in the Thermal Processing of Cocoa Butter Fat as Examined Using Wide Angle X-ray Scattering (WAXS) , 2003 .

[24]  R. Müller,et al.  Correlation between long-term stability of solid lipid nanoparticles (SLN) and crystallinity of the lipid phase. , 1999, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[25]  M. Avrami Granulation, Phase Change, and Microstructure Kinetics of Phase Change. III , 1941 .

[26]  N. Garti,et al.  Crystallization and polymorphism of fats and fatty acids , 1988 .

[27]  M. Schubert,et al.  Thermal analysis of the crystallization and melting behavior of lipid matrices and lipid nanoparticles containing high amounts of lecithin. , 2005, International journal of pharmaceutics.

[28]  H. Moghimi,et al.  A lamellar matrix model for stratum corneum intercellular lipids. I. Characterisation and comparison with stratum corneum inter-cellular structure , 1996 .

[29]  J. Toro‐Vázquez,et al.  Crystallization of cocoa butter with and without polar lipids evaluated by rheometry, calorimetry and polarized light microscopy , 2005 .

[30]  C. P. Tan,et al.  Differential scanning calorimetric analysis of edible oils: Comparison of thermal properties and chemical composition , 2000 .

[31]  S. Gohla,et al.  Comparison of wax and glyceride solid lipid nanoparticles (SLN). , 2000, International journal of pharmaceutics.

[32]  C. E. Stauffer Fats and oils , 1996 .

[33]  D. Small The Physical Chemistry of Lipids , 1986 .

[34]  J. A. Solís-Fuentes,et al.  Determination of the predominant polymorphic form of mango (Mangifera indica) almond fat by differential scanning calorimetry and X-ray diffraction , 2005 .

[35]  M. Avrami Kinetics of Phase Change. II Transformation‐Time Relations for Random Distribution of Nuclei , 1940 .