Ijaz Hussain, Political and Legal Dimensions of Indus Water Treaty (Book Reviews)

Of the many issues that the partition of India in 1947 did not address in time, and were left to worsen the relations between India and Pakistan, the issue of riparian rights was only next in importance to the issue of Kashmir. In many respects the two issues have direct bearing on each other as well, as some important rivers emanate from Indian-held Kashmir. As the time passes more and more historians are coming to the conclusion that the massacre at the time of partition, the uprooting of more than 12 million people from their native homes, horrendous violence against women, burning and looting, etc, all owe mainly to the colonial administration that failed to ensure peaceful transition to two independent countries. No less than a person than a former Prime Minister of Great Britain, Winston Churchill, described the attitude of the then British government as the ‘biggest escape of human history’. In its urge to get rid of Indian responsibility, the government of Prime Minister Clement Atlee, showed extraordinary haste in relinquishing its responsibilities without ascertaining that the partition of a country of a subcontinental size would involve a huge amount of work. It required taking into consideration all administrative and security aspects so that the two countries could move along their independent journey as good neighbours. Unfortunately, the failure of the British government, both in London and, through its viceroy, in Delhi, left a number of issues unsettled, which the two independent countries have been trying to resolve for the last seven decades. Moreover, with the passage of time, new factors emerged which further complicated the original issues.

Taste Masking of Azithromycin and Clarithromy by Adsorption of Nanoparticles and Microspheres Approach

The obnoxious bitter taste and low aqueous solubility is the major issue for paediatric oral suspension. Most of the infants and children cannot tolerate the bitter taste of the drug and vomit out which leads to suboptimal therapeutic value. It is the most challenging task for the scientists to mask and fabricate a palatable oral formulation during preformulation stage. In this study a taste masked dry suspension of Azithromycin (AZ) and clarithromycin (CL) were prepared by using two different approaches i-e physisorption and microsphere techneques. In both techneques a fixed amount of drugs were treated with varied ratios of titanium dioxide nanoparticles (TNP) and Eudragit L100 (EUD) were physically mixed to get the optimized taste masked nanohybrid and microspheres followed langmuir adsorption isotherm and microsphere by solvent evaporation method. The morphology and particle size of the starting materials including TNP (70-200nm ±10.0nm), azithromycin (5±5.0μm), clarithromycin (8.5±5.0μm), nanohybrids of AZ and CL(10±5.0μm) and microspheres of azithromycin and clarithromycin (80±5μm) were confirmed by using scanning electron microscopy and zeta sizer. The crystallinity and the physical state of both processed and unprocessed drugs were confirmed by P-XRD (powder X-ray diffraction) and differential scanning calorimetry (DSC) techniques. The unprocessed drugs showed endotherms peaks that represent their melting point while the processed drugs after physical mixture with that of TNP or EUD showed its endotherm to lower scale of melting point due to the physical mixture. The crystallinity and physical state was also cross confirmed by comparing the P-XRD peak intensities, no change was observed in the XRD pattern except low peak intensities which confirmed physical interaction of both drug and polymer. The FTIR (Fourier transformed Infrared) spectra of unprocessed and optimized drugs (AZN, AZM, CLN and CLM) were investigate for any possible interactions. It was observed from the spectrum that the drug(s) and excipient were physical mixture as no distinct peaks were matched. The adsorption equilibrium study confirmed that least quantity of TNP (10mg & 8.64mg) was adsorbed onto the surface of AZ and CL respectively, which surround a layer around the drug molecule and inhibit the release of bitter drug in mouth cavity. The adsorption was also confirmed from SEM micrograph in which a white sheet of TNP was seen on the surface of AZ and CL. It was noticed and confirmed that four times greater quantity of Eudragit L 100 polymer (EUD) were consumed for the fabrication of taste masked optimized microsphere of CL and AZ, In contrast the TNP used for taste masking of AZ and CL was negligible. Furthermore It was also evident from the langmuir adsorption isotherm that TNP showed high adsorption equilibrium in azithromycin when compared to clarithromycin. The taste masking and palatability of produced nanohybrids and microspheres were evalated by sequential test followed by panel testing using human volunteer. The azithromycin and clarithromycin nanohybrids batche (AZN-7, CLN-6) and its formulations batches (AZN- F6 & CLN-F3) as well as microspheres batches (AZM-4, CLM-4 and AZM-F4, CLM-F3) were approved and declared the most palatable, taste masked optimized nanohybrids, microspheres and its formulations. The In-Vitro dissolution study was conducted for unprocessed selected drug, optimized formulation containing optimized nanohybrids and microspheres. The marketed drug was used as a standard for comparitive dissolution study. The dissolution study were performed at both saliva (6.8) and intestinal pH (7.4) medim. Both optimized formulation showed negligible or retarded release in 20 minutes (< 10%) at saliva pH whereas more than 95% dissolution was acheived with in 30 minutes at intestinal pH (7.4). It was concluded that TNP have the capability of masking the bitter taste by inhibiting the release of bitter drug compounds The stability study for optimized formulations of AZ and CL was conducted for both reconstituted and dry sample, stored at 2-8°C and 40°C respectively. All the stability tests including active content (97%), flow property, pH, re-dispersion and viscosity showed no signaficant change through out its shelf life. In addition acute and subacute oral toxicity was conducted for optimized formulations containing nanohyrids (AZN-F6 & CLN-F3). The results showed no mortality, toxicity or not adversely affected any vital organ during or after taking dose so the formulation was declared safe. In summary the extreme bitter taste of azithromycin and clarithromycin in dry suspension dosage form was effectively masked by new and novel approach of physisorption by selecting (TNP) which is biocompatable having high margin of safety and compared the results with that taste masked formulations of both drug crafted with microsphere techneques using (EUD). The results showed that the bitter taste was completely masked by using several fold lesser quantity with out affecteing its stability and bioavailility when compared with the results of formulations prepared by microsphere techneque using EUD polymer which was used four times of the drug quanity.