CHAPTER ONE
INTRODUCTION AND LITERATURE REVIEW
1.1 Introduction
Lubricants are additives which reduce friction and are an essential component of a drug formulation. Lubrication is frequently a requisite ensuring the achievement of a good pharmaceutical manufacturing (Morin and Briens,2013).
Pharmaceutical lubricants as excipients are added to the tablet formulation in a very small quantity (usually 0.25%-5%w/w), to prevent sticking of tablets to the die cavity as well as sticking of capsules to dosators and tamping pins (Li and Wu, 2014).
Without lubricants, tablets cannot be produced. However some uncertainty exists in the definition of a lubricant because glidants and anti-adherents perform the same purpose (Majekodunmi and Matthew, 2014). These inter-related groups of tablet excipients are used in tablet production to promote granule flow and prevent powder adhesion to punch faces and minimize die wall friction respectively (Adedokunet al., 2014; Adedokun and Itiola, 2013).
Although magnesium stearate and stearic acid are the most frequently used lubricants in the pharmaceutical industry, there are other lubricants in use as well (Li and Wu, 2014). Lipids (oily and fatty substances) by their nature exert lubricity between surfaces that are in relative motion. It is therefore explicable that when applied in carefully regulated amounts, they could develop the lubricating efficiency of lubricants in general. (Shiparet al., 2013) showed that unlike magnesium stearate, which delays disintegration and dissolution of the active ingredient, the fatty acid esters promotes a reduction in disintegration time. Fatty acid esters have better-quality as lubricant than magnesium stearate because the tablets containing them have better stability and are free from biological problems such as viral contamination as a result of very low moisture content of the granules containing the fatty acid esters compared with those of other lubricants.
Coconut oil or copra oil (common name) (Cocosnucifera), (Fam.Arecaceae),IsipMbakara in Ibibio, Idi-agbon in Yoruba, Aku-Oyinbo in Igbo, Mosara in Hausa (Aiyeloja and Bello, 2006), belongs to the class of the fixed oil, and is a commercially available edible (vegetable) oil extracted from the kernel or meat of matured coconuts harvested from the coconut palm. Coconut oil has various applications in food, medicine, and industry. Chemical composition of coconut oil includes lauric saturated C12 (46.64-48.03%), myristic saturated C14 (16%), palmitic saturated C16 (9.5%), Oleic monounsaturated C18 (6.5%), free fairly low fatty acid content (0.15-0.25%). All chemical compositions are within the limit of official standard for edible coconut oil (Amaoet al., 2015). Coconut oil also contains lipid-oily and fatty substances with a high percentage of saturated hydrocarbons mainly glyceride of caprylic acid and glyceride of lauric acid and by their nature exert lubricity over surfaces encountered with (Amaoet al., 2015). It is therefore that when applied in carefully regulated amount they will improve the lubrication efficiency in lubricants used in tableting.
In terms of powder or granule flow, unit operations can be aided and the flowability of blends can be improved by lubricants. An example, is the blending of active pharmaceutical ingredients (APIs) of a small particles with other excipients, the adhesion force can extensively reduce the powder flowability between particles by increasing inter-particle friction; poor flow can cause insufficient mixing of the blends (content uniformity) and rat-holing in the hopper of a tablet press (segregation issue), impacting both product quality and operation. To overcome these issues, lubricants are added (glidants) to enhance powder flow by reducing inter-particle friction.
- Classification of lubricants
Classification of lubricants varies based on the approach such as; the source and the nature. The source of lubricant can be classified into natural and synthetic. Despite many efforts to substitute natural additives for synthetic additives, synthetic additives for formulations are inevitably being used in tablet products, which are widely used in the pharmaceutical and health functional food industries, and are associated with various problems occurring during processes, including sticking, which a disc (a plate with which a mixture for compression comes into contact) sticks to a surface of puncture in a tablet compression machine. Among these synthetic additives, stearic acid or magnesium stearate which is most widely used as a lubricant shows excellent lubricant performance even when it is used in an amount of 0.5-1% based on the total weight of a mixture for compression, and also assists in improving the flowability of the mixture. Also, if the flowability of a pharmacological mixture needs to be improved, a glidant such as silicon dioxide or talc is widely used.
The natural lubricant can prevent a sticking phenomenon from occurring in direct compression. In addition, according to the present invention, the flowability of a mixture for direct compression can be improved by a dry granulation process using a roller compactor, and a natural tablet having ensured productivity can be provided. As used herein, the term “natural lubricant” is a material having a lubricant effect, which is prepared by physical extraction process without carrying out a chemical extraction process or a chemical reaction. In the present invention, pharmaceutically acceptable lubricants, for example, including, but not limited to, magnesium stearate, polyethylene glycol, talc, calcium stearate, microcrystalline cellulose, etc., are defined as chemical synthetic products (hereinafter referred to as synthetic lubricants), and the inventive natural lubricant material substituting for such synthetic lubricants is defined as natural lubricant (Strickland, 1959).
Carter (2006) showed that two major types of lubricants exist, such as hydrophilic which are generally poor lubricants, no glidant or anti-adherent properties and hydrophobic; which are the most widely used lubricants today.
Hydrophobic lubricants are generally good lubricants and are usually effective at relatively low concentrations. Many also have both anti-adherent and glidant properties. For these reasons, hydrophobic lubricants are used much more frequently than hydrophilic compounds. Tableting materials need lubrication to some degree. Although, only a few drugs and excipient do not require lubrication i.e., Acetyl Salicylic Acid (ASA), starch and microcrystalline cellulose. Of all the lubricants in use, “magnesium stearate” is the extensively used lubricant in the pharmaceutical industry. Even though it is employed in low concentrations, it is often the cause of many problems experienced in solid oral dosage forms. The determination of the level of lubricants to use and the manner in which they are incorporated into a batch is important if concentrations are too low, or distribution and mixing times are inadequate, problems can occur. Some examples include; sticking, capping, picking, punch filming, binding in the die cavity.
If distribution and mixing times are greater or concentrations are too high, potential problems include; increase in rate of dissolution, decrease in tablet hardness, inability to compress into tablets, increase in tablet disintegration time.
1.1.2 Naturallubricants
Natural tablet lubricants exist as either semi solid fats or oils. Oils is the generic expression for substances belonging to extensive series of bodies of diverse chemical character, all of which have the common physical property of being fluid either at the ordinary temperature or at temperatures below the boiling-point of water. Examples of natural lubricants are the fluid fixed oils or fatty oils (e.g. olive oil), the soft fats which may be fluid in their country of origin (e.g. coconut oil, palm oil), the hard fats (e.g. tallow), the still harder vegetable and animal waxes (e.g. carnauba wax, beeswax), the odoriferous ethereal (essential) oils, and the fluid and solid volatile hydrocarbons – mineral hydrocarbons – found in nature or obtained from natural products by destructive distillation.
The common characteristic of all these substances is that they consist principally, in some cases exclusively, of carbon and hydrogen. They are all readily inflammable and are practically insoluble in water. Those formed naturally within the vegetable and animal organisms, viz.: fixed oils, fats and waxes, and essential, ethereal or volatile oils.
