The document refers in this context specifically to the handbook on pharmaceutical excipients from which document D15 represents an excerpt (see D1, page 27, lines 23-26). Document D15 as well as document D16, which represents the corresponding section of the subsequent edition of the handbook, mention calcium stearate as a pharmaceutical excipient related to magnesium stearate (see D15, page 281, right column, under "18. Related Substances"; see D16, page 306, right column, under "18. Related Substances").
The Board observes, however, that document D15 and its update in document D16 (see D15, page 281, right column, under "14. Safety" and "15. Handling Precautions"; see D16, page 306, right column, under "15. Handling Precautions") evidently refer to precautions aimed at avoiding harm from excessive inhalation of magnesium dust when handling the bulk substance. As pointed out by the appellant and not contested by the respondent, the claimed subject-matter relates to pharmaceutical compositions for pulmonary administration in which only limited amounts of magnesium stearate are inhaled. The mentioned handling precautions against excessive inhalation are therefore not considered to affect the skilled person's expectation regarding the suitability of magnesium stearate for use as an alternative to the surface modifiers described in document D1. In this context the concern mentioned in document D30 reflects in the Board's view the general desirability to minimize the amount of low soluble excipients introduced in the lung, but does not discourage the skilled person from using magnesium stearate as an alternative to the surface modifiers mentioned in document D1.
Natural resins are complex substances that are produced as oxidation products of essential oils and act in response to ecological interactions. Resins are applied in different areas including in the pharmaceutical sector as excipients in the formulation of various dosage forms [1, 2]. The functions of pharmaceutical excipients including resins are to control the release of drugs, maintain stability, alter the bioavailability, improve the therapeutic efficacy of drugs, and decrease unwanted side effects [3, 4]. Unfortunately, there are very few natural resins that have been explored for use as additives in pharmaceuticals. For instance, rosin is among the very few resins that are applied for pharmaceutical applications [5, 6]. Thus, natural products are still the potential sources for the further investigation of resins that can be applied to the pharmaceutical sector.
Natural resins can be directly obtained either from plants or animals [7]. They are, however, mostly extracted and isolated from plants [8]. Like other natural additives, natural resins have many advantages over chemically synthesized substances; they are safer, less expensive, biodegradable, and widely available [9, 10]. Natural resins could be thus a good choice to be used as excipients in various pharmaceutical dosage forms, like in the preparation of microcapsules, as film formers, coating materials, and matrix formers in solid dosage forms, as well as in drug delivery systems [11, 12].
There had been limited studies conducted before on the use of natural resins in general and Boswellia resins in particular as a pharmaceutical ingredient. A few studies revealed the potential use of the crude Boswellia gum resins as binding agents and drug release retardants [15, 16]. Nevertheless, the crude resin extracts of Boswellia species contain the potent bioactive compounds and Boswellic acids [17, 18]. Therefore, it is not appropriate to be used as an additive in the formulation of drug products owing to the fact that pharmaceutical excipients should be pharmacologically inert at used amounts. Considering this limitation, the isolated resin from the oleo gum resin of Boswellia rivae Engl was investigated after separating the bioactive Boswellic acid contents using a standard method. Thus, the physicochemical properties of the neutral resin were evaluated for its potential use as an excipient in the formulation of drugs.
Pharmaceutical excipients like resins can be obtained through chemical synthesis, directly from natural sources, or by chemical modification of natural products [32]. In this study, neutral resin was isolated from oleo gum resin, which was extracted from a plant called Boswellia rivae. The extract was a resinous, pale yellow irregular powder in appearance. The yield was found to be relatively fair, and thus reasonable for use as a pharmaceutical excipient. Moreover, the resin powder was devoid of the bioactive secondary metabolites, revealing its pharmacological inertness which is the main desired property of excipients used in drug formulations [33].
The solubility of pharmaceutical excipients can affect the delivery of the drugs from the dosage forms either by increasing or decreasing the release of the drugs from the dosage device [36]. The resin powder was found to be very slightly soluble in water even if it was freely soluble in various organic solvents. Less water-soluble polymers are usually employed in the formulation of medicine to sustain the release of drugs [37]. Besides, the powder exhibited swelling to some extent in water at a neutral pH value which allows slow diffusion of the candidate drugs after dissolution. On these grounds, Boswellia resin could be a potential excipient to be applied in the formulation of various modified-release products acting as a matrix former and microencapsulating agents.
 38c6e68cf9