Solubilization of Hydrophobic Drugs - Essay Example

Hydrophobic Drugs Introduction Solubilisation of hydrophobic drugs is a commonly encountered problem in screening analysis of new drugs together with the preparation as well as its development. There are a number of ways to counter this challenge in order to improve the solubilisation of the hydrophobic drugs to improve their bioavailability. The bioavailability is dependent on many aspects. The key ones include the drug permeability through lipophilic membranes and the solubility in an aqueous solution (Jouyban, 2010) It is only the solubilised drugs molecules can be absorbed to the site of drug action. Drugs must be in aqueous form in order for them to be absorbed at the site of absorption. The techniques used in the include Nano-crystal technique, Nano-emulsions technique, Miceller solubilisation, Hydrotrophy and Solid dispersion among others (Siepmann, Siegel and Rathbone, 2012) These techniques are as discussed below. 1. Nanocrystal technique It is a carrier-free colloidal delivery system. Nanocrystal system is a feasible drug delivery method to dissolve the poor soluble drugs due to the ease in preparation and the overall applicability. The particle size of colloid ranges from 100 to 1000nm (Yeo, n.d.) The word nanocrystal means a crystalline state of distinct particles. They production can either be partially or totally amorphous i. Precipitation technique The hydrophobic drug is dissolved in an organic solvent. The solution produced is then added into an aqueous solvent (Miscible non-solvent) under agitation. This results in rapid super saturation, leading to fast nucleation and precipitation. This method works taking the advantage of differences in the solubility of the drugs in various miscible solutions or liquids. Stabilizers are usually added to prevent the formation of tiny particles due to impulsive aggregation of particles (Yeo, n.d.) There are some parameters used to get uniform nanoparticles. These parameters that need to be optimized include the stirring rate, drug content, antisolvent to solvent volume ratio and temperature ii. Pearl milling technique Pearl milling nanocrystal technique, suspension is formed using a shear pearl mill. The mill contains a milling motor, a milling chamber, recirculation chamber and milling pearls. In this technique, the milling chamber (containing milling pearls) is filled with water, surfactants and drugs. Using the motor, the pearls rotate at a high speed. Using high shear forces, the hydrophobic drugs are comminuted to nano-sized crystals. Fine nanocrystal suspensions can be achieved through pearl milling progress. It is possible to realize the results within some hours to days depending on the intended particle size for routes of administration (parenteral administration), drug quantities and hardness The process can be performed in two ways, batch or recirculation modes. Minute particles with no batch-to-batch difference can be gotten after optimum formulation and progress is accomplished iii. High-pressure homogenization technique This technique employs a high pressure with a piston-gap homogenizer. Suspensions containing water and surfactant go through a very narrow opening at a very speed; the energy generated by the particles collision and cavitation forces is sufficient to comminute the hydrophobic drugs into nano-sized particles. This strategy is best utilized for those drugs that poorly soluble in all forms of media like aqueous and non-aqueous (Caruso and Ariga, 2010) In this process, the suspension is pumped into a thin gap. High energy is generated as the suspension is pumped through the narrow gap. Basing on the Bernoulli’s equation, the pressure of the suspensions concurrently drops keep the constant energy. As the raw material leaves the gap, the pressure rapidly normalizes and the vapour bubbles shrink forcefully. The energy created in this rapid process is sufficient to break down the hydrophobic drugs particles into nano-size 2. Nano-emulsions technique It is a heterogeneous method involving two immiscible fluids in one of the liquid is dispersed as droplets in the other. This technique comprises of oil droplets put in an aqueous solution and stabilized by surfactant particles. Stable nano-emulsion of hydrophobic drugs is accomplished with enough shelf stability and no clear flocculation. The benefit of the this technique include better drug loading and greater bioavailability (Liu, 2008) The oil droplets act as the receptacle for hydrophobic drugs. Saturated and unsaturated fatty acids including soybeans and fatty acid esters are the commonly used oil molecules in this process. The surfactants have a key role in stabilizing the nanoemulsions. Combination of different amphoteric surfactants is used to improve stability and manage the droplets size of nanoemulsions. The strategies used to produce Nano-emulsions include, spontaneous emulsification, mircrofluidization, HPH, and ultra-sonication. Microfluidization utilizes a high-pressure pump to power the suspensions through numerous micro channels in the central chamber of microfluidizer. This method normally leads to the creation of nano-emulsions with narrow size distributions In HPH, rough emulsion prudence nano-emulsions due to disruptive forces generated by lot of pressure. The number of cycles and the homogenization pressure are the main factors that influence the size distribution and the droplet size of nano-emulsions in the process of nano-crystal formation (Caruso and Ariga, 2010) Ultra-sonication on the other hand works by disrupting microscopic droplets using the ultrasound energy. Even though the process is simple and easy, it leads to a non-heterogeneous distribution of nano-droplet sizes. The ultrasound energy produced is high enough to cause structural damage to the ingredients 3. Miceller solubilisation: This technique utilizes the use of surfactants to aid the dissolution performance of hydrophobic drugs. The surfactants work by lowering the surface tension and increase the solubility of lipophilic drugs. Surfactants are also used to successfully stabilize the drug suspensions. Between the ranges 0.05 and 0.10 per cent is the critical micelle concentration. Upon exceeding this range, micelle formation begins to form in a process known as micellisation. The process boosts the solubility of hydrophobic drugs. The frequently used non-ionic surfactants include polyoxyethylated glycerides, polysorbates, lauroyl macroglycerides among others. There are two categories of micelles. They are mixed micelles and polymeric micelles (Mahato and Narang, 2012) i. Polymeric micelles Amphiphilic polymers gather together to form polymeric micelles, which are nanoscopic (nano-sized) supra-molecular core-shell structure. Polymeric micelles are usually safe for parenteral administration depending on the solubilizing agent used in its preparation. The technique is normally used to increase the drug potent of hydrophobic drugs. The compatibility of hydrophobic drug and the basics of polymeric micelles help in the drug solubilisation (Mahato and Narang, 2012) The success of this strategy relies on the ability of polymeric micelles to circulate in blood for a long of time and elude the host defence thereby slowly releasing the drug to the blood. Polymeric micelles work best by building up at the tumours and other sites of diseases. The impede p-glycoprotein at drug-resistant tumours blood, gastrointestinal track and brain barrier in order to offer a means of overpowering drug resistance and improve the absorption of the drugs in the blood system and the brain 4. Hydrotrophy It is another technique for the preparing a solution for water soluble drugs. In this method, a large amount of second solute is added to increase the solubility of another. Inn this way, it increases the increases the solubility of the hydrophobic drug in water due the presence of additives. This method is closely associateted with the complexation where there is poor interaction between the hydrotropic agents such as urea, sodium acetate, sodium benzoate, sodium alginate and hydrophobic drugs (Mahato and Narang, 2012) The solute contains alkali metals from different organic acids. The agents of hydrotropic are ionic organic salts. Those that improve the solubility are known as “salt in” and while additives or salts that lower the solubility are referred to as “salt out” the solute ii. Mixed micelles When dispersed in water, bilayers are formed from chains of phospholipids due to the effect of the temperature, water content and the chemical structure. Mixed Micelles (MM) is formed due to the interaction between the lipophilic drugs and the micelles. The Mixed Micelles formed is commonly referred to as swollen micelles. The addition of alcohol, salt and other additives influences the degree of penetration into the co-solubilisation. The kinetics of the micelles is determined by the dissolution, the new formation of micelles and the micelle-monometer 5. Solid dispersion This technique was Sekiguchi and Obi in early 1960 who examined the creation and the dissolution performance sulphonamide drug. The most frequently hydrophilic carriers of this method include Docusate sodium, polyethylene glycols among others (Caruso and Ariga, 2010) Hydrophobic drug is dispersed in a very soluble solid hydrophilic matrix. The matrix improves the solution of hydrophobic drug. This method gives rise to either molecular level mixing commonly known as solid solution or eutectic, a non-molecular mixing (Caruso and Ariga, 2010) The availability of the drug in microcrystalline state, increased wettability and the creation of high free energy amorphous state of the product through the solid dispersion development lead to improvement of drug solubilisation (Liu, 2008) Conclusion Solubility of drugs is an essential aspect that influences the therapeutic efficacy as well as well as its formulation, hence the most crucial element in the formulation development. The drugs dissolution is the rate of determine step for parenteral delivery of hydrophobic drugs. The solubility is also another fundamental necessity for the development and formulation of various dosage forms of various drugs References Caruso, F. and Ariga, K. (2010). Modern techniques for nano- and microreactors/-reactions. 1st ed. Berlin: Springer-Verlag. Jouyban, A. (2010). Handbook of solubility data for pharmaceuticals. 1st ed. Boca Raton: CRC Press. Liu, R. (2008). Water-insoluble drug formulation. 1st ed. Boca Raton, FL: CRC Press. Mahato, R. and Narang, A. (2012). Pharmaceutical dosage forms and drug delivery. 1st ed. Boca Raton, FL: CRC Press. Siepmann, J., Siegel, R. and Rathbone, M. (2012). Fundamentals and applications of controlled release drug delivery. 1st ed. New York: Springer. Thassu, D., Deleers, M. and Pathak, Y. (2007). Nanoparticulate drug delivery systems. 1st ed. New York: Informa Healthcare. Williams, R., Watts, A. and Miller, D. (2012). Formulating poorly water soluble drugs. 1st ed. New York, NY: AAPS Press. Yeo, Y. (n.d.). Nanoparticulate drug delivery systems. 1st ed. Read More