DESC:FIELD OF THE INVENTION
The present invention relates to the Boswellic acid Phytosomes are unique forms of boswellic acid complexed with Soya lecithin- Asparagus synergy complex that clinically demonstrated enhanced absorption and bioavailability. In particular, the present disclosure relates to the Boswellic acid Phytosomes developed by optimized synergy complex of Asparagus- Soya Lecithin by solid dispersion technology. The present disclosure further relates to the effect of phospholipids alone and in combination with common surfactants (Tween 80, Asparagus Saponin, Cremophor) on the solubility of boswellic acid. Another invention relates to Soya Lecithin as a phospholipid and Saponin of Asparagus as a surfactant is optimized for Boswellic acid Phytosomes formulation.

BACKGROUND OF THE INVENTION
Boswellic acid (pentacyclic triterpene, a carboxyl group and at least one other functional group) extract of Boswellia serrata is one of the most scientifically investigated plant compound for anti-inflammatory action. However, Boswellic acid’s health-supporting properties depend on its bioavailability. Hence Boswellic acid Phytosomes are unique forms of boswellic acid complexed with Soya lecithin that clinically demonstrated enhanced absorption and bioavailability as compared to standard boswellic acid as an extract.

Saponin is a group of compounds widely distributed in the plant kingdom. Due to their amphiphilic characteristic structure, saponins have high surface activity and self-assembly properties and can be used as a natural biosurfactant. Therefore, saponin has become a potential solubilizing carrier in poor characteristics. Number of studies have found that when standard drug or Phytochemical combine with saponins, their solubility or bioavailability are improved. This phenomenon may be due to a synergistic mechanism and provides a potentially novel concept for a good therapeutical effect.

Soya lecithin is a phospholipid that enhances solubility and absorption of various phytochemicals like curcumin, Silymarin, gingerol etc. Boswellic acid Phytosomes developed by optimized synergy complex of Asparagus- Soya Lecithin by solid dispersion technology. Solubility study in different PH is analyzed compared with standard boswellic acid.
Bioavailability is a major hurdle in the translation of the preclinical potential of many botanical extracts into therapeutic effects, especially for those whose active ingredients show poor water solubility and strong tendency to self-aggregate. This is the case for many polyphenols and triterpenoid acids. Phospholipid-based delivery systems have been developed to improve the oral availability of these compounds and the extracts that contain them. Among different strategies, a Phytosome delivery form has emerged as a promising “dietary” candidate.

The mechanism by which Phytosome improves the absorption of plant phenolics and terpenoids is not known. Presumably, two processes are involved, namely improving their dispersion in the intestinal fluids, and “chaperoning” them into the enterocytes by lecithin. Extracts of the gum resin of Boswellia serrata, a traditional ayurvedic medicine, have become popular in Western countries. In vitro assays, animal studies and pilot clinical trials have established a potential for B. serrata gum resin extracts to alleviate a variety of inflammatory conditions that include inflammatory bowel disease, rheumatoid arthritis, osteoarthritis and asthma.

Standard Boswellic acid is converted into Phytosomes by adding Soya Lecithin as a phospholipid & further effectiveness of solubility and absorption is developed by adding a synergy form of natural surfactant Asparagus saponin. Only a few natural drugs have been formulated and are available in the market as Phytosomes. With a wide range of applications of Phytosomes, numerous studies are undergoing and lots more are expected in the forthcoming years. The techniques used for such formulations are patentable and highly profitable.

US20220362184A1 invention describes a gut-protective composition comprising boswellic acid, at least one pH modifier, wherein the composition exhibits enhanced dissolution. The composition as described herein may be comprised of about 5 to 95% of boswellic acid. The said composition is stable and exhibits improved bioavailability. The invention also provides a process for preparation of the said composition, wherein boswellic acid and pH modifier are mixed well by optionally adding at least one or more excipient and processed to get granular powder. The composition may be further formulated into solid, semi solid or liquid dosage forms, for administration to human or animals. The compositions described herein exhibit gut-protective effect in conditions of colitis as well as microbial infections.

AU2022291492A1 discloses Highly bioavailable compositions and related methods of improving the bioavailability of one or more compounds are disclosed. The compositions and methods disclosed herein may be employed to improve the bioavailability of poorly soluble or poorly bioavailable ingredients (e.g., curcumin) in a subject (e.g., a mammal).

Fitoterapia (Volume 84, January 2013, Pages 89-98) Enhanced absorption of boswellic acids by a lecithin delivery form (Phytosome®) of Boswellia extract (Hüsch, Jan, et al. ) discloses The anti-inflammatory potential of Boswellia serrata gum resin extracts has been demonstrated in vitro and in animal studies as well as in pilot clinical trials. However, pharmacokinetic studies have evidenced low systemic absorption of boswellic acids (BAs), especially of KBA and AKBA, in rodents and humans. This observation has provided a rationale to improve the formulation of Boswellia extract. We present here the results of a murine comparative bioavailability study of Casperome™, a soy lecithin formulation of standardized B. serrata gum resin extract (BE), and its corresponding non-formulated extract. The concentration of the six major BAs [11-keto-ß-boswellic acid (KBA), acetyl-11-keto-ß-boswellic acid (AKBA), ß-boswellic acid (ßBA), acetyl-ß-boswellic acid (AßBA), a-boswellic acid (aBA), and acetyl-a-boswellic acid (AaBA)] was evaluated in the plasma and in a series of tissues (brain, muscle, eye, liver and kidney), providing the first data on tissue distribution of BAs. Weight equivalent and equimolar oral administration of Casperome™ provided significantly higher plasma levels (up to 7-fold for KBA, and 3-fold for ßBA quantified as area under the plasma concentration time curve, AUClast) compared to the non-formulated extract.

International journal of research in medicine, Formulation and Evaluation of Phytosome Drug Delivery System of Boswellia Serrata Extract (Sahu, A. R., & Bothara, S. B. (2015)) discloses Boswellic acid is a Phytoconstituent obtained from Shallaki (Boswellia Serrata). Oral use of this drug has some limitations like Low bioavailability, High first pass Metabolism. Conventional treatment include tablet, Capsule; Available in market, have high dose Quantity and Frequency. The aim of the present investigation was to formulate boswellic acid loaded Phytosome for improved delivery. Phytosomal formulations were developed using different concentration of Cholesterol (1-3%) and ethanol (20-40%) then optimized and characterized. Particle size, entrapment efficiency and vesicular shape were determined by Malvern Zetasizer, Ultracentrifugation and Scanning Electron Microscopy, respectively. Particle size varied from 179 to 514.8 nm depending on the concentrations of Cholesterol and ethanol. Entrapment efficiencies were exhibited of 39.8 ± 3.7% to 74.2 ± 4.3 %, where it increased with concentration of cholesterol and ethanol increased. Photomicrographs revealed that optimized Phytosomes were spherical in shape and uniform in size. Based on minimum particle size and maximum entrapment efficiency E6 (2% of Cholesterol concentration and 40% of ethanol concentration) was selected as optimization Phytosomal formulation.

Journal of Functional Foods (Volume 79, April 2021, 104405) Enhanced absorption of curcuminoids and 3-Acetyl-11-keto-ß-boswellic acid from fenugreek galactomannan hydrogel beadlets: A natural approach to the co-delivery of lipophilic phytonutrients (Abhilash, Maliakkal Balakrishnan, et al.) discloses Simultaneous oral delivery of bioactive molecules with enhanced bioavailability is of great significance, especially when delivered from single beadlets. Here, we report the formulation, characterization, and pharmacokinetic properties of two poorly bioavailable lipophilic phytonutrients with synergistic effects, curcuminoids and 3-Acetyl-11-keto-ß-boswellic acid (AKBA), following their co-delivery using fenugreek dietary fiber (Galactomannans)-based hydrogel beadlets (CGM-BSW).

SUMMARY OF THE INVENTION
The present invention relates to the Boswellic acid Phytosomes are unique forms of boswellic acid complexed with Soya lecithin - Asparagus synergy complex that clinically demonstrated enhanced absorption and bioavailability. In particular, the present disclosure relates to the Boswellic acid Phytosomes developed by optimized synergy complex of Asparagus - Soya Lecithin by solid dispersion technology. The present disclosure further relates to the effect of phospholipids alone and in combination with common surfactants (Tween 80, Asparagus Saponin, Cremophor) on the solubility of boswellic acid. Another invention relates to Soya Lecithin as a phospholipid and Saponin of Asparagus as a surfactant is optimized for Boswellic acid Phytosomes formulation.

The effectiveness of any herbal medication is dependent on the delivery of an effective level of the therapeutically active compound. Several limitations exist in their dissolution and bioavailability when administered orally on the other side absorption topically. Phytosomes are recently introduced herbal formulations that are better absorbed than standard extracts. Most of the biologically active constituents of plants are polar or water-soluble molecules, but as increased with active constituent’s concentration, solubility and bioavailability can decrease. However, water-soluble phytoconstituents like flavonoids, tannins, glycosidic aglycones, etc. are poorly absorbed either due to their large molecular size which cannot absorb by passive diffusion or due to their poor lipid solubility; severely limiting their ability to pass across the lipid-rich biological membranes, resulting poor bioavailability.

DETAILED DESCRIPTION OF THE INVENTION:
Detailed Description of the Invention While this specification concludes with claims particularly pointing out and distinctly claiming that, which is regarded as the invention, it is anticipated that the invention can be more readily understood through reading the following detailed description of the invention and study of the included examples.
The following is a detailed description of embodiments of the present disclosure. The embodiments are in such detail as to clearly communicate the disclosure. However, the amount of detail offered is not intended to limit the anticipated variations of embodiments; on the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the present disclosure as defined by the appended claims.

Unless the context requires otherwise, throughout the specification which follow, the word “comprise” and variations thereof, such as, “comprises” and “comprising” are to be construed in an open, inclusive sense that is as “including, but not limited to.”

Reference throughout this specification to “one embodiment” or “an embodiment” means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, the appearances of the phrases “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.

The headings and abstract of the invention provided herein are for convenience only and do not interpret the scope or meaning of the embodiments.

Various terms are used herein. To the extent a term used in a claim is not defined below, it should be given the broadest definition persons in the pertinent art have given that term as reflected in printed publications and issued patents at the time of.
Phospholipid delivery system is one of the lipid-based vesicular delivery systems which can be used for the encapsulation of drugs and plant-derived (Botanical) nutraceuticals such as polyphenolic compounds. Phytosomes are advanced forms of herbal formulations that are better absorbed, and as a result, produce better bioavailability and actions than conventional herbal extracts. They are produced by a patented process whereby the standardized plant extract or its constituents are bound to phospholipids, mainly phosphatidylcholine, producing a lipid-compatible molecular complex. This Phyto-phospholipid complex (Phytosomes) resembles a little cell. Phytosomes exhibit better pharmacokinetic and pharmacodynamic profiles than conventional herbal extracts. Phytosomes technology has been effectively used to enhance the bioavailability of many popular herbal extracts including milk thistle, Ginkgo biloba, grape seed, green tea, hawthorn, ginseng, etc., and can be developed for various therapeutic uses or dietary supplements.

Lecithin is a phospholipid that enhances the solubility and absorption of various phytochemicals like curcumin, Silymarin, gingerol, etc. Solid dispersion complex of Boswellic acid soya lecithin, Boswellic acid Asparagus and Boswellic acid Soya Lecithin: Asparagus saponin synergy form evaluated for solubility & absorption. Boswellic acid Phytosomes developed by optimized synergy complex of Asparagus- Soya Lecithin by solid dispersion technology. Solubility and Absorption study in different PH is analyzed compared with standard boswellic acid. Stock solution prepared for solubility analysis. Boswellia Phytosomes is an extract of Boswellia gum resin that has been complexed with phospholipids to improve its absorption. Clinical studies in the product contains Boswellia Phytosomes that support a healthy inflammatory response and symptomatic relief in arthritis patients.

Phytosomes are recently introduced herbal formulations that are developed by different complex technology and as a result produce better solubility, absorption and bioavailability. In recent days, most of the prevailing diseases and nutritional disorders are treated with natural medicines. Several plant extracts and phytoconstituents, despite having excellent bioactivity in vitro demonstrate less or no in vivo actions due to their poor lipid solubility or improper molecular size or both, resulting in poor absorption and bioavailability. Phytosomes are better absorbed and utilized and as a result, produce better results than conventional herbal extracts owing to the presence of phosphatidylcholine which likely pushes the phytoconstituent through the intestinal epithelial cell outer membrane, subsequently accessing the bloodstream Phytosomes improved pharmacokinetic and pharmacological parameter which in result can advantageously be used in the treatment of the inflammatory disease, acute and chronic liver disease of the toxic metabolic or inflammatory infective origin or metabolic disease like diabetes.

First objective is to build up boswellic acid design by optimization of two independent variables like Soya Lecithin and Asparagus saponin with the response of solubility and dissolution. Modified complex is compared and analyzed with standard boswellic acid for its characterization, physical evaluation and micrometrics.

In additional objective, Boswellic acids have long been considered to be the main bioactive components of Boswellia serrata, and many preclinical studies have confirmed their bioactivities. In particular, recent mechanistic studies have validated the capacity of the boswellic acid’s family to modulate the physiological response to various challenges, but preliminary pharmacokinetic studies in animals and humans have highlighted the poor oral absorption of boswellic acid due to its solubility. To overcome this problem, Boswellic acid Phospholipid delivery system has been formulated with a novel mixture of boswellic acids from Boswellia serrata with soya lecithin and Asparagus Saponin as surfactant/ PH modifying agent, taking advantage to improve the therapeutically effect by Phytosomes technology platform to optimize their absorption.

Examples
1. Method preparation of Boswellic acid Phytosomes
Active constituents Soya Lecithin: Asparagus saponin ratio Total concentration (%)
Boswellic acid 0.5:0.5 2-5
Boswellic acid 0.5:1 2-5
Boswellic acid 1:0.5 2-5
Boswellic acid 1:1 2-5

2. Solubility Enhancement in Phytosomes vs Standard
Active constituents
Of Synergy blend Concentration (%) Water solubility improvement % Improvement in gut Absorption
Boswellic acid 65% 2-5 Insoluble Poor
Soya Lecithin 2-5 22% 28%
Asparagus saponin 2-5 26% 10%
BA-Phytosomes 2-5 46% 35%

3. Micromeritic property Enhancement
Micromeritics properties Boswellic acid 65% Soya Lecithin Asparagus saponin BA-Phytosomes
Angle of Repose 41.25 32-33 33-35 31-33
Carr’s index 18.54 16-18 16-18 14-16
Hausner Ratio 1.26 1.20-1.23 1.21-1.24 1.18-1.20

4. Stability study and Physical evaluation of Optimized batch
Physical evaluation BA-Phytosomes
(0 Day) BA-Phytosomes
(3 months) Pharmacopeial Standards
% Release in 45 min 99.98 98.13 Compliance
Moisture content Less than 1 % Less than 1 % Compliance
Disintegration time % 90-120 sec 90-120 sec Compliance
Compressibility index 14-16 14-16 Compliance
Enhanced Solubility 0.5 mg/ml 0.5 mg/ml Compliance

,CLAIMS:1. A boswellic acid Phytosomes formulation for enhancing absorption and bioavailability.
2. The boswellic acid Phytosomes formulation as claimed in claim 1, wherein boswellic acid phytosomes are unique forms of boswellic acid complexed with soya lecithin- asparagus synergy complex.
3. The boswellic acid Phytosomes formulation as claimed in claim 1, wherein Boswellic acid Phytosomes developed by optimized synergy complex of Asparagus- Soya Lecithin by solid dispersion technology.
4. The boswellic acid Phytosomes formulation as claimed in claim 1, wherein effect of phospholipids alone and in combination with common surfactants (Tween 80, Asparagus Saponin, Cremophor) on the solubility of boswellic acid.
5. The boswellic acid Phytosomes formulation as claimed in claim 1, wherein Soya Lecithin as a phospholipid and Saponin of Asparagus as a surfactant is optimized for Boswellic acid Phytosomes formulation.
6. A method of preparation of Boswellic acid Phytosomes by solid dispersion technology comprises of;
a. Weigh the appropriate amounts of Boswellic acid, Asparagus extract, and Soya Lecithin according to the desired formulation ratio.
b. Dissolve or disperse the components in a suitable solvent or blend them directly.
c. Mix thoroughly to ensure homogeneity of the mixture.
d. Use solid dispersion techniques such as spray drying or hot melt extrusion to obtain a solid dispersion of Boswellic acid, Asparagus extract, and Soya Lecithin.