ABSTRACT
One of the basic differences between modern medicine (Allopathic) and indigenous medicine (like Unani) is that the earlier deals with a particular constituent/component/moiety while systems like Unani medicine relies on holistic approach. Converting entire crude form of a drug into a dosage form poses problems to a pharmaceutical scientists which result into a large dosage size, increased dosing regimen, inadequate mixing of different crude drugs and patient non-compliance (geriatrics, pediatrics and non-conscious). Now we are laden with techniques like nanotechnology (e.g., NE technology). By judicious exploration of technology we can think of dosage forms that can address the challenges being faced and also complying with formula of ancient scriptures (Qrabadeen). This may be successfully explored in liquid dosage forms like Jushanda, Khasanda, Haleeb, Sharbat and other types of sayyal. It can also be explored for external dosage forms (liquid and semi-solid). A genuine effort and ability to think out of the box would definitely pave the way for amalgamation of NE technology with Unani system of medicine.

INTRODUCTION

The belief that natural medicines are much safer than synthetic drugs has gained popularity in recent years and led to tremendous growth of phyto-pharmaceutical usage. On the other hand ancient scriptures of different civilization (Greek, Indian, Chinese etc.) are abundant with well proven usage of different herbs for the treatment of mankind and animals too. Unani system of medicine is one of them and well structured and documented. In recent patent controversies of turmeric and Neem, antique literatures of Unani system (Qarabadeen) played a major role in strengthening our case.
One of the basic differences between a modern medicine (Allopathic) and indigenous medicines (including Unani) is that the earlier deals with a particular constituent/component/moiety while the other relies on holistic approach. Converting entire crude form of a drug into a dosage form doesn’t offer much space to a pharmaceutical scientists which result into a large dosage size, increased dosing regimen, inadequate mixing of different crude drugs and patient non-compliance (geriatrics, paediatrics and non-conscious).Previously herbal drugs could not attract scientists towards the development of novel drug delivery systems due to processing, standardising, extracting and identification difficulties. Other limitations were instability in acidic pH, liver metabolism etc. which led to drug levels below therapeutic concentration in the blood resulting in less or no therapeutic effect. Now we are equipped with modern sophisticated techniques (analytical, formulation and clinical). Novel technologies used in drug delivery are well proven for their curative potential for particular disease by targeting exactly the affected zone inside a patient’s body and transporting the drug to that area. It is also advantageous in delivering the herbal drug at predetermined rate and delivery of drug at the site of action which minimizes the toxic effects with the increase in bioavailability of the drugs. In novel drug delivery technology, control of the distribution of drug is achieved by incorporating the drug in carrier system or in changing the structure of the drug at molecular level. For last one decade many novel carriers such as liposomes, nanoparticles, phytosomes and implants have been reported for successful modified deliveryof various herbal drugs e.g. curcumin, quercetin, silybin, ginkgo etc. Incorporation of herbal drugs in the delivery system also aids to increase in solubility, enhanced stability, protection from toxicity, enhanced pharmacological activity, improved tissue macrophage distribution, sustained delivery and protection from physical and chemical degradation.By judicious exploration of technology we can think of dosage forms that can address the challenges being faced, complying with formulas of Qrabadeen and also establish its authenticity clinically. In Table 1 some herbal drugs have been enlisted that are being used in Unani and Ayurvedic systems of medicine. Preclinical and clinical efficacies of most of them have also been tested. But usually herbal medicine has relied on tradition that may or may not be supported by empirical data. Evidence-based verification of the efficacy of herbal medicinal products/botanicals is still lacking in general. However, in recent years, data on evaluation of the therapeutic and toxic activity of herbal medicinal products became available.
Nanonization possesses many advantages, such as increasing compound solubility, reducing medicinal doses, andimproving the absorbency of herbal medicines compared with the respective crude drugs preparations. Nanoemulsion (NE) is one of them, has a potential to carry both hydrophilic and lipophilic components of crude drugs. It is a type of colloidal system with particles varying in size from 10 nm to1000 nm (Ratnam, Ankola et al., 2006).
Generally, NE consist ofoil phase, surfactant and aqueous phase which represented the oil droplet size in the range of 50-200 nm dispersed in the aqueous phase using the appropriate surfactant and their concentration. Currently, there are growing interest of essential oil which are prepared in term of NEs such as curcumin (Ahmed, Li et al. 2012), eucalyptus oil (Saranya, Chandrasekaran et al. 2012) and lemonoil (Rao and McClements 2012). In this article we will discuss the potential of Nanoemulsion technology to deal with different drugs/dosage forms of Unani system of medicine.

NANOEMULSION IN UNANI SYSTEM
NEs are the emulsions of O/W or W/O type having the size range of few microns/nanometres. They areprepared by using the surfactants which are considered safefor the human use and approved by the FDA. These types ofemulsions have higher surface area and hence can easily penetrate through biological membrane. They are also non toxic and nonirritant in nature and can be used in the animals and veterinary (Shah, Bhalodia et al. 2010)purpose. NE can be prepared by the high(Lieberman, Rieger et al. 1998)pressure homogenization and micro-fluidisation technique.
Reducing droplet sizes to the nanoscale leads to some very interesting physical properties, such as optical transparency (Figure 1) and unusual elastic behaviour. In the world of nanomaterials, NEs hold great promise as useful dispersions of deformable nanoscale droplets that can have remarkably varying flow properties and optical properties ranging from opaque to nearly transparent. Moreover, it is very likely that NE will play an increasingly important role commercially, since they can typically be formulated using significantly less surfactant than is required for nano structured lyotropicmicro emulsion phases. Such phases are actually quite different (Mason, Graves et al. 2006). Lyotropic liquid crystals are equilibrium structures comprised of liquids and surfactant, such as lamellar sheets, hexagon- ally packed columns, and wormlike micellar phases, that form spontaneously through thermodynamic self assembly. By contrast, NEs do not form spontaneously; an external shear must be applied to rupture larger droplets into smaller ones. Compared to microemulsion phases, relatively little is known about creating and controlling NE. This is primarily because extreme shear, well beyond the reach of ordinary mixing devices, must be applied to overcome the effects of surface tension to rupture the droplets into the nanoscale regime (Mason, Graves et al. 2006). In Table 2 some commercially available NEs have been shared that further authenticates its applicability in drug delivery.
NE technique can be explored for both types of liquid dosage forms (Sayyal), internal and external. They are more demanding in case of oral drug delivery considering the bulky size of dosage units. Dispensing single drugs (Mufradaat) into NEis not a big challenge. But compound drugs (Murakkabat) possess a big challenge. Nearly all different forms of drugs can be converted into NE like solid (Jamid), semisolid (neemjamid) and liquid (sayyal) like curcuminpowder and various oils (roghan badaam, babchi oil, neem oil etc). Solid drugs (Jamid mufradaat) are first converted into suitable oil or aqueous phase by solubilising into suitable oil while oils are taken as such or by solubilising into oil. The overall drug loading into dosage form (NE) depends upon the solubility of drug in the oil. It has successfully addressed the bioavailability problems of curcumin. Today curcumin has been widely acknowledged globallyas a”wonder drug of the future” because of its great potential abilities to prevent and treat a wide spectrum of incurable andchronic diseases. However, the major problem limiting the exploitation of its potentially valuable therapeutic effects is its low bioavailability (Dandekar, Jain et al. 2010). In practice, only very low or undetectable levels of curcumin can be achieved in blood byoral administration of curcumin. The low bioavailability of curcumin has been attributed to its very low aqueous solubility, tendency to degrade in the gastrointestinal tract in the physiological environment, high rate of metabolism, and rapid systemic elimination. The low bioavailability of curcumin has sofar limited its medical use. It has been suggested that a person isrequired to consume large doses (about 12-20g/day) of curcumin inorder to achieve its therapeutic effects on

Table 1. A collection of commonly used herbs in Ayurvedic and Unani system of medicine. Botanical names and family are also mentioned. Click here to view full image

Table 2. Commercial nanoemulsion formulations along with their manufacturers . Click here to view full image

Figure 1. General method of preparation of Emulsion (a, b, c and d). Difference in transparency between Emulsion and Nanoemulsion are also evident in the figure. Click here to view full image

the human body (Dandekar, Jain et al. 2010). That means one has to swallow 24 to 40 curcumin capsules of 500 mg each. These doses are considered to be too high, and therefore, not feasible to be incorporated in clinical trials due to unbearable after-taste to the palate, possibility of giving rise to nauseatic feeling and perceived toxicity issues. One of the solution to this conundrum was the development of NE of curcumin (Rachmawati, Budiputra et al. 2014).
On the other hand components of a compound drug vary in nature like solubility (lipophilic/hydrophilic), consistency and susceptibility to different conditions. Here we havealso a good alternative in the form of NE. Lipophilic drugs/extracts can be solubilised in a suitable oil carrier and any of the oil can also be taken as a carrier if it suitable dissolves other lipophilic components. Similarly hydrophilic components can be separately converted into an aqueous medium. Both the differently natured solvents can be transformed into a single transparent NE by the techniques mentioned above. But formulation optimization process of compound drug is exhaustive as compared to single drugs.
If dare to think out of the box, two systems of medicine can also be amalgamated. A synergistic NE was formulated using two drugs of different origin Tea tree oil and Itraconazole for vaginal candidiasis (Mirza, Ahmad et al. 2013). The dual loading of Itraconazole and tea tree oil in a single formulation seems promising as it elaborated themicrobial coverage. Despite being low solubility of Itraconazole in tea tree oil, a homogeneous, transparent and stable solution of both was created by co-solvency using chloroform. Complete removal of chloroform was authenticated by Gass chromatography-mass spectroscopy and the oil solution was used in the development of NE which was further translated into a gel bearing thermo sensitive properties.

CONCLUSIONS

Above evidences put a strong rational for the exploration of NE technology for drugs and dosage forms being used in Unani system of medicine. By implication of these modern technologies therapeutic efficacy and acceptability of these indigenous medicines can be improved along with acceptable dosage sizes, dosing regimen, and patient compliance.

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