Preformulation is a branch of pharmaceutical sciences that utilize biopharmaceutical principles in the determination of physicochemical properties of drug substance. It is the first step in the rational development of dosage forms of a drug substance. It can be defined as an investigation of physical and chemical properties of a drug substance alone and when combined with excipients.
Preformulation studies constitute the delicate connection between the two major groups of scientists that is those at the drug discovery end and those at the drug delivery end. It is for the drug discovery group to bring out a novel molecule. In drug discovery, the scientists identifies interesting drug compounds, drug target and delivery mechanism with the potential for development into products,characterize compound and their targets and also provide fundamental information on target biological system.
Drug discovery involve synthesis and extraction which is the process of identifying new molecules. After that, the chemical entity discovered enter biological screening and pharmacological testing to explore the pharmacological activity and therapeutic potential of compounds. Then the drug enter preclinical testing which involve toxicology and safety testing to determine the potential risk a compound poses to humans and the environment,involve use of animals, tissue culture or other test system. Preclinical drug development provide data on the safety and efficacy of the product.
Subsequently, the drug enter preformulation studies. The goals of preformulation studies are to choose correct form of drug substance, evaluate physical properties and generate a thorough understanding of the material’s stability under various conditions, leading to optimal drug delivery system.Steps in preformulation process of pharmaceutical research are evaluating stability, physicochemical properties, mechanical properties, dissolution properties, plasma protein binding and excipients compatibility.
In preformulation process,stability test is done to evaluate drug stability at elevated temperature,on exposure to light and humidity for solid state while for solution, the drug is tested in term of its stability in solvent, stability at varying pH range and also stability to the light. This stabilty data will be used in designing dosage form or formulation which is said to be stable and meet expected specification for identifying, purity, quality and strength throughout their defined storage period at specific storage condition.
Physicochemical properties of drugs are also evaluated such as the molecular structure and weight, color, odour, particle size,shape and cristallinity as well as melting point. Thermal analysis profile of drug is determined to measure the changes in chemical and physical properties of a sample as a function of temperature and the test employ thermogravimetry, differential scanning calorimetry or differential thermal analysis method.
Besides that, the hygroscopic potential of drug and the absorbance spectra using UV and IR is also determined. Next the solubility profile of drug is established as solubility is important for drug dissolution and subsequent absorption. It will affect the bioavailabilty of dosage form besides the ionisation constant and partition coefficient. The last aspect of physichochemical properties is polymorphism. Polymorphism is the ability of solid material to exist in more than one crystalline structure. Polymorphism will affect the stability of drug as drug with different polymorph has different physical and chemical properties and this will cause change in solubility and affect bioavailability. Many physicochemical properties change with the change in internal structure for example melting point, hardness, optical density, crystal shape, vapor pressure and et cetera.
After physicochemical properties, mechanical properties of drug is also determined such as the bulk density, compressibility and powder flow. This data will aid in designing solid dosage form later on in formulation aspect. Other than thats,steps in preformulation are to studies the dissolution properties, plasma protein binding and excipient compatibility of the drug. Dissolution properties will influence the bioavailability of drug while excipient compatibility study is crucial to aid the formulation scientist to determine the best excipients to be used in the formulation of drug to ensure the stability of the finished product.
Formulation group has the task to make the drug into deliverable form with the aid of the data provided by the preformulation scientists. Drug formulation involve the combination of drug substance or active ingredients with drugs excipients to get the desired drug products. Drug excipients are any inactive ingredient that is intentionally added to therapeutic product but not intended to exert therapeutic effects at the intended dosage. It is added to aid drug manufacturing process and to maintain drug stability. The desired drug product is then scaled up to be produced in large quantity.
The drug products then enter phase I,II and III clinical trials to astablish its safety, effectiveness, side effects,toxicity and the most appropriate dosage regimen by testing it in healthy volunteers and patient with the disorder being studied but before the drug is tested in human, the manufacturer must obtain and Investigational New Drug (IND) designation from FDA and the application is based on pre-clinical test data conducted in animal.. After the drug product has passed stage III clinical trial, the drug need to be registered through New Drug Application (NDA) or Biologics License Application.
Once the drug is approved and registered by FDA, it can be marketed but the clinical trial still continue in stage IV or post-marketing surveillance to identify any problems that did not occur in phase I,II or III, such as those that take a long time to appear and those that rarely occur.
