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Sustained release from inert wax matrixes I: drug-wax combinations.

The melting and energy characteristics of several drug-wax combinations were investigated using differential scanning calorimetry. The phase diagrams of binary mixtures of tripelennamine hydrochloride and tolazoline hydrochloride with carnauba wax and castor wax showed no eutectic formation and gave no indication that a significant interaction was involved. However, in tripelennamine mixtures, a slight depression in the drug melting point was observed at around 50% concentration. For ternary systems, i.e., drug, carnauba wax, and stearyl alcohol, thermograms of samples prepared by a fusion method differed slightly from those obtained with mixtures formulated by dissolving all ingredients in chloroform and evaporating the solvent. However, the location of the peak of each component remained essentially the same. A plot of melting point versus concentration of each compound showed insignificant changes in melting point and indicated that no interaction was occurring. The phase diagrams suggested that the combinations are strictly physical and that it is the physical characteristics, such as the hardness and composition of the core and drug particle size, that influence the release or dissolution of drug from the waxy matrix.

Chemistry, Pharmaceutical↗

Wax lipid secretion and ultrastructural development in the egg-waxing (Gene's) organ in ixodid ticks.

Gene's organ, the egg-waxing organ of ticks, performs an essential function in females by coating the eggs with a waterproofing layer during oviposition, which prevents desiccation of the embryo, ensuring its viability. The organ is a target for control agents and a potential site of virus replication involving trans-oval transmission of arboviruses. The organ is a complex dermal gland, developed to an elaborate degree. The external appendage, the horns, is an evertable balloon-like cuticular sac which manipulates the eggs and coats them in wax. Wax passes through pores in the cuticle from the internal, sub-cuticular lumen. Gene's organ develops in synchrony with oogenesis and oviposition. This paper describes the development of the gland cells and formation of the intra-cuticular lumen and its ultrastructure during engorgement and oviposition in ixodid ticks. The structural basis for wax secretion in Gene's organ is also described.

Animals↗

Release from or through a wax matrix system. III. Basic properties of release through the wax matrix layer.

Release property of reservoir device matrix tablet was examined. Wax matrix layer was prepared from physical mixture of lactose and hydrogenated castor oil to obtain basic release properties. Release process showed zero order kinetics in a steady state after a given lag times, and could be divided into two stages. The first stage was the formation process of water channel by dissolving the soluble component in the wax matrix layer. The lag time was considered to be the time required forming water channel and the time begun to release drug through the wax matrix layer at the same time. The lag time obtained by applying the square root law equation was well connected with the amount of matrix layer and mixed weight fraction of component in matrix layer. The second stage was the zero order release process of drug in the reservoir through the wax matrix layer. The release rate constants were calculated by taking into accounts of the thickness of matrix layer and permeability coefficient, and were well connected with the amount of matrix layer and mixed weight fraction of component. Also it was suggested that the tortuosity of matrix layer could be expressed by a function of the porosity defined by the mixed weight fraction.

Chemistry, Pharmaceutical↗

Release from or through a wax matrix system. V. Applicability of the square-root time law equation for release from a wax matrix tablet.

To obtain basic and clear release properties, wax matrix tablets were prepared from a physical mixture of drug and wax powder at a fixed mixing ratio. Properties of release from the single flat-faced surface, curved side surface, and/or whole surface of the wax matrix tablet were examined. Then tortuosity and the applicability of Higuchi's square-root time law equation were examined. The Higuchi equation well analyzed the release processes of different release manners. However, the region fitted to the Higuchi equation differed with the release manner. Tortuosity obtained with release from the single flat-faced surface and curved side surface was comparable with that obtained with the release from a reservoir device tablet, whereas tortuosity obtained with release from the whole surface was larger. As the wax matrix tablets were prepared at a fixed mixing ratio, their internal structures should be similar. Therefore changes in the matrix volume or volume fraction with release were examined, and an extra volume where dissolved drug stray becomes large with release time in the case of release from the whole surface. These factors should be taken into account for evaluation of applicability and release properties. Furthermore, the entire release process should be analyzed using a combination of the square-root time law and other suitable equations in accordance with release manner or condition.

Tablets↗

A novel bifunctional wax ester synthase/acyl-CoA:diacylglycerol acyltransferase mediates wax ester and triacylglycerol biosynthesis in Acinetobacter calcoaceticus ADP1.

Triacylglycerols (TAGs) and wax esters are neutral lipids with considerable importance for dietetic, technical, cosmetic, and pharmaceutical applications. Acinetobacter calcoaceticus ADP1 accumulates wax esters and TAGs as intracellular storage lipids. We describe here the identification of a bifunctional enzyme from this bacterium exhibiting acyl-CoA:fatty alcohol acyltransferase (wax ester synthase, WS) as well as acyl-CoA:diacylglycerol acyltransferase (DGAT) activity. Experiments with a knock-out mutant demonstrated the key role of the bifunctional WS/DGAT for biosynthesis of both storage lipids in A. calcoaceticus. This novel type of long-chain acyl-CoA acyltransferase is not related to known acyltransferases including the WS from jojoba (Simmondsia chinensis), the DGAT1 or DGAT2 families present in yeast, plants, and animals, and the phospholipid:diacylglycerol acyltransferase catalyzing TAG formation in yeast and plants. A large number of WS/DGAT-related proteins were identified in Mycobacterium and Arabidopsis thaliana indicating an important function of these proteins. WS and DGAT activity was demonstrated for the translational product of one WS/DGAT homologous gene from M. smegmatis mc(2)155. The potential of WS/DGAT to establish novel processes for biotechnological production of jojoba-like wax esters was demonstrated by heterologous expression in recombinant Pseudomonas citronellolis. The potential of WS/DGAT as a selective therapeutic target of mycobacterial infections is discussed.

Acinetobacter↗

Studies on the structure of the plant wax nonacosan-10-ol, the main component of epicuticular wax conifers.

The main component presents in the epicuticular waxes of needles of Pinus halepensis and the most of conifers, the secondary alcohol nonacosan-10-ol, has been investigated by X-ray diffraction and differential scanning calorimetry. The results obtained from these physical techniques permitted to establish a definitive structural model of the molecular arrangement of this wax, basically in good agreement with the model formulated by other authors from theoretical formulations. Biological implications of the proposed structure have been also formulated.

Calorimetry↗

Mechanism of the anisotropic dimensional change of the wax pattern prepared by the softened wax technique. (1) Relationship between recovery and crystal orientation.

In order to obtain information on the behavior of wax pattern distortion and to reveal its mechanism, the following experiments have been conducted: measurements of fundamental properties including distribution of molecular weight, crystal structure, phase transition, and viscosity, and investigation of the crystal orientation and recovery phenomena. If the wax is deformed plastically at higher temperatures, transformation appears to be a smooth transition from an isotropic distribution of the crystal orientation to an arranged structure. In the case of uniaxial compression, the c-axes are rearranged parallel to the compressed direction and the b-axes and a-axes are randomly oriented in the plane normal to the c-axes. This preferred orientation is due to the crystal rotation. The degree of preferred orientation increases with the increase in compression ratio over all temperatures between 35 degrees C and 55 degrees C. Above 45 degrees C, the degree of orientation decreases with an increase in temperature despite the equal compression ratio. From this fact, the degree of orientation is associated with the crystallinity at deformation temperatures as well as the degree of deformation. The preferentially oriented specimen expands greatly in the direction parallel to the molecular chain axis and shrinks to a great extent in the direction perpendicular to the chain axis. This anisotropy is caused mainly by the recovery. Moreover, the extent of recovery is associated closely with the degree of the preferred orientation. The dimensional change due to the recovery is extraordinarily large (30 to 40%) in comparison with the normal thermal expansion from room temperature to 45 degrees C (approximately 1.2%). This large extent of recovery is explained by the rubber-like deformation in the amorphous region.

Crystallization↗

Final report of the safety assessment of Acacia catechu gum, Acacia concinna fruit extract, Acacia dealbata leaf extract, Acacia dealbata leaf wax, Acacia decurrens extract, Acacia farnesiana extract, Acacia farnesiana flower wax, Acacia farnesiana gum, Acacia senegal extract, Acacia senegal gum, and Acacia senegal gum extract.

These ingredients are derived from various species of the acacia plant. Only material derived from Acacia senegal are in current use according to industry data. The concentration at which these ingredients are reported to be used ranges from 9% in mascara to 0.0001% in tonics, dressings, and other hair-grooming aids. Gum arabic is a technical name for Acacia Senegal Gum. Gum arabic is comprised of various sugars and glucuronic acid residues in a long chain of galactosyl units with branched oligosaccharides. Gum arabic is generally recognized as safe as a direct food additive. Little information is available to characterize the extracts of other Acacia plant parts or material from other species. Acacia Concinna Fruit Extract was generally described as containing saponins, alkaloids, and malic acid with parabens and potassium sorbate added as preservatives. Cosmetic ingredient functions have been reported for Acacia Decurrens Extract (astringent; skin-conditioning agent--occlusive) and Acacia Farnesiana Extract (astringent), but not for the other Acacias included in this review. Toxicity data on gum arabic indicates little or no acute, short-term, or subchronic toxicity. Gum arabic is negative in several genotoxicity assays, is not a reproductive or developmental toxin, and is not carcinogenic when given intraperitoneally or orally. Clinical testing indicated some evidence of skin sensitization with gum arabic. The extensive safety test data on gum arabic supports the safety of Acacia Senegal Gum and Acacia Senegal Gum Extract, and it was concluded that these two ingredients are safe as used in cosmetic formulations. It was not possible, however, to relate the data on gum arabic to the crude Acacias and their extracts from species other than Acacia senegal. Therefore, the available data were considered insufficient to support the safety of Acacia Catechu Gum, Acacia Concinna Fruit Extract, Acacia Dealbata Leaf Extract, Acacia Dealbata Leaf Wax, Acacia Decurrens Extract, Acacia Farnesiana Extract, Acacia Farnesiana Flower Wax, Acacia Farnesiana Gum, and Acacia Senegal Extract in cosmetic products. The additional data needed to complete the safety assessment for these ingredients include (1) concentration of use; (2) identify the specific chemical constituents, and clarify the relationship between crude Acacias and their extracts and the Acacias and their extracts that are used as cosmetic ingredients; (3) data on contaminants, particularly relating to the presence of pesticide residues, and a determination of whether Acacia melanoxylon is used in cosmetics and whether acamelin (a quinone) and melacacidin (a flavin) are present in the Acacias that are being used; (4) skin sensitization study (i.e., dose response to be determined); (5) contact urticaria study at use concentration; and (6) ultraviolet (UV) absorption spectrum; if there is significant absorbance in the UVA or UVB range, then a photosensitization study may be needed. It was also noted that other data may be needed after clarification of the chemical constituents of the Acacia-derived ingredients.

Acacia↗