Formulation of microparticles of cimetidine and their invitro charterisation by dirrefent techniques e.g SEM, FTIR and XRD and then invivo evaluation of the selective formulation using normal human volunteers for the pharmacokinetic parameters evaluation.

In this study the self-microemulsifying drug delivery systems (SMEDDS)of poorly water-soluble drugs (anticancer, antifungal, antihypertensive, NSAIDs, antipsychotics etc) will be developed to increase the drug solubility and absorption in GIT. SMEDDS have been known for their numerous advantages like spontaneous formation, ease of manufacture, stability, and improved solubilization, faster release rates and better availability in the blood, which leads to lesser drug dose, lower cost, and reduced stomach irritation and toxicity; thus ultimately improving drug acceptance by the consumers. SMEDDS will be prepared and evaluated in comparison with other commercially available medicines for blood concentration in mice. Thus, safe and highly cost effective formulations of water insoluble drugs will be developed which will be new hope for patients and an attraction for pharmaceutical industry.

In this study the self-microemulsifying drug delivery systems (SMEDDS)of poorly water-soluble drugs (anticancer, antifungal, antihypertensive, NSAIDs, antipsychotics etc) will be developed to increase the drug solubility and absorption in GIT. SMEDDS have been known for their numerous advantages like spontaneous formation, ease of manufacture, stability, and improved solubilization, faster release rates and better availability in the blood, which leads to lesser drug dose, lower cost, and reduced stomach irritation and toxicity; thus ultimately improving drug acceptance by the consumers. SMEDDS will be prepared and evaluated in comparison with other commercially available medicines for blood concentration in mice. Thus, safe and highly cost effective formulations of water insoluble drugs will be developed which will be new hope for patients and an attraction for pharmaceutical industry

Biomaterials and Its Applications in Medicine/Drug Delivery. Nanocomplexes formation and their In Vitro Characterization.

In Vivo Studies in Animal Models.

PEGYLATED PROTAMINE – RECOMBINANT HUMAN INTERLEUKIN 24 AND DOXORUBICIN NANOPARTICLES FOR SINGLE COMBINATION THERAPY OF CANCER

Impaired wound-healing in diabetics can lead to life-threatening complications, such as limb amputation, associated in part with excessive matrix metalloproteinase- (MMP-) mediated degradation of collagen and other matrix constituents. In the current study, hydrogel 3-D network based on Hyaluronic acid, Curcumin and natural polymers will be formulated impaired wound healing and acceleration of wound healing process dramatically. 

The practice of ‘polypharmacy’ or Multiple Drug Therapy, especially in patients with multiple complications, has resulted in some serious clinical drug–drug interactions (HemaIswarya and Doble, 2006; Nadler et al., 2003). This is one of the major causes of withdrawal of drugs from the market during the past few years (Wienkers and Heath, 2005). The most common mechanism underlying these drug-drug interactions is the inhibition of cytochrome P450 enzyme. CYP450 superfamily is responsible for the metabolism of nearly 90% of the drugs in humans both at the hepatic and intestinal level. Among the identified CYP isoforms till date, five human CYP isoforms (CYP1A2, CYP2C9, CYP2D6, CYP2E1 and CYP3A4) are rather important as they are responsible for 80% of the CYP mediated metabolism (Daly, 2004; IngelmanSundberg, 2004; Shimada et al., 1994). Inhibition or induction of these CYPs isoforms can lead to adverse drug reactions as well as therapeutic failure in certain cases.

Herbal preparations nowadays are increasing being consumed along with modern drugs, particularly in the western countries, with a purpose to reduce the side effects or toxicities associated with modern drugs or to provide synergistic/additive pharmacological effects (Graham et al., 2008). There is a common belief that since these herbal medications are natural, they are safe for human consumption. However, a number of reports have been published in the past signifying that many constituents of these natural products can cause dramatic alteration in the pharmacokinetic properties of the co-administered drugs, thus affecting their efficacy as well as safety. For instance, several components of grapefruit juice like bergaptin, a furanocoumarin derivative and other flavanoids are reported to be responsible for the inhibitory effect of grapefruit juice on CYP3A4 (Ho et al., 2001) and alter the pharmacokinetics of a number of clinically available drugs like midazolam, cyclosporine, nifedipine (Bailey et al., 1998). Constituents of pomegranate juice are also found to be strong inhibitors of CYP3A4 and CYP2C9 catalytic activity (Hidaka et al., 2005; Nagata et al., 2007). Decreased plasma levels of cyclosporine have been observed when it is co-administered with St. John’s wort due to induction of CYP450 enzymes involved in the metabolism of cyclosporine, resulting in incidences of kidney transplant rejection (Barone et al., 2000). Dietary isoflavones, popularly known as phytoestrogens, are widely distributed in the Leguminosae family. Hence, the purpose of our study is to find how FMN and BCA affect the regulatory mechanisms of hepatic CYP enzymes utilizing FDA approved specific probe substrates for major CYP isoforms in humans (CYP1A2, CYP2C9, CYP2D6, CYP2E1 and CYP3A4) and rats (CYP1A2, CYP2C11, CYP2D4, CYP2E1 and CYP3A2).

Herbal medicines are gaining importance very quickly because they are derived from nature, thus, they are perceived to be free of side effects. However, their co-administration with conventional medicines can have life-threatening consequences. For such herbal medicines, it is essential to determine the pharmacokinetics and the drug’s cytochrome P450 (CYP) enzyme and metabolic profile in order to predict their possible interactions with other conventional drugs. The most popular, trusted and frequently using brands of herbal medicines for cough and flu in Pakistan are; Toot siyah (Hamdard), Surficol syrup (Qarshi) and Qarshi Johar Joshanda (Qarshi). These all are considered promising drug candidate from herbal source to treat respiratory problems and flu. So, these brands should be investigated for the inhibitory effects on CYP enzyme activities, in order to predict its possible interactions with CYP drug substrate via CYP inhibition to establish its safety.

The aim of study is to investigate the CYP-mediated drug interactions of the most trusted herbal products for safety measures and to predict and minimize the ADRs and other serious consequences from herb-drug interactions by suggesting its proper management. It is to establish confidence in physicians and prescribers, where poly-pharmacy is concerned.

Numerous drug delivery systems for conveyance of drugs into the body (via different routes) are continuously being explored in order to treat and combat the ever increasing disease rates (Raffa et al., 2018). In the treatment regime, most commonly used route of drug delivery has been  oral route as it has many perks including highest patient compliance, cost effectiveness, minimum requirements for sterility, comfort of self- administration, a cascade  of options to construct dosage forms and luxury of self –administration by the patient (Goldberg et al., 2003).  For achieving optimized drug levels in the  circulation for the drug to show  therapeutic activity, firstly it has to pass through  biological membrane and be transported in the blood supply to be bioavailable (Behrens et al., 2002). However few challenges are faced in the oral administration of the drug. The main problematic areas are of drug dissolution, solubility of the chemical moities and the drug permeability (Alany, 2017). Approximately, 40% of the modern day drug molecules show poor aqueous solubility that provides major hindrance in the efficient oral delivery (Lipinski, 2002). Drug solubilization in the gastrointestinal cavity is the rate-limiting step for absorption of such drugs. Since majority of the recently developed drugs exhibit lipophilic character, hence they show limited dissolution in the gastric fluids that leads to limited absorption and low permeability of drugs through the gastric mucosal membrane.

 To overcome all these problems different strategies can be adopted such salt formulation, micro-ionization, inclusion in cyclo-dextrin, entrapment in micro/nanoparticles, loading in solid dispersion, solubility in lipid-based systems, mixed micelles, use of silica based mesoporous materials have been employed to enhance drug solubility (Vemula et al., 2010).

Modification of the conventional drug delivery systems of the existing drug entities into a new dosage forms can significantly enhance the efficacy of the drug. A few drugs have an ideal concentration spectrum that provides the maximum therapeutic effect while drug concentrations beyond the range of this spectrum can prove to be sub-therapeutic or toxic for the body (Hamada et al., 2012). The exceptionally moderate advancement in the treatment regimen calls for a dire need to implement a multidisciplinary research approach for the conveyance of optimal drug therapy (Orive et al., 2004). Conventional dosage forms involve the formulation of the drug into an appropriate form such as a compressed pill for the oral administration or an alternative for intravenous delivery. These dosage forms are known to have some serious limitations in terms of higher dosage requirement, below average drug efficacy, poor bioavailability, toxicity and side effects (Wilczewska et al., 2012).

Novel drug delivery systems (NDDS) are being developed to overcome hindrances encountered by conventional modes of drug delivery systems to enable health experts to provide optimal treatments (Barbe et al., 2004).

 NDDS have a number of advantages such as enhanced drug efficacy, targeted delivery, low toxicity, improved patience compliance, controlled or sustained delivery of the drug, increased drug stability, ease of drug solubilization and a maximum number of treatment options. Newly introduced systems include phyto-somes, lipo-somes, nano-particles, dendrimers, liquid crystals, etho-somes, micro-spheres, pro-niosomes, nio-somes, hydrogels and self- emulsifying drug delivery systems (Yue et al., 2010). Lipid- based systems are preferable over other systems as the drug is kept in the solubilized state until complete absorption thus conquering the hindrance of slow dissolution rates of the drug (Porter et al., 2007).  Among the lipid based systems, SEDDS is the most promising as it not only improves the drug solubilization but also enhances the drug particle diffusion across the gastrointestinal tract, membrane permeability and lymphatic absorption due to  presence of surfactants, mediums and oils (Pouton et al., 2010).  

Self-emulsifying drug delivery systems can be defined as isotropic systems of natural or synthetic oils, solid or liquid surfactants, or one or more hydrophilic co-solvents or surfactants (Tang et al., 2008). The first step in the preparation of SEDDS is agitation and then dilution in aqueous media such as in gastrointestinal fluids that render the system to form oil in water emulsion. The principle involved here is speculated to be the combined action of specificpharmaceutical excipients with low free energy. The droplets that are formed on the formation of emulsion are responsible for the increased surface area, rapid release of drug in the dissolved form or mixed micelle and transportation of drug through the unstirred water layer to the GI membrane for absorption (Gursoy et al., 2004). Another advantage of SEDDS is that the lipid SEDDS increase the lymphatic drug transport by facilitating the lipoprotein formation and increasing intestinal lymphatic liquid flux which enhances overall drug uptake and hence increases bioavailability of drug.