Issues to Consider in Tablet Formulation of a New non-Sedating Antihistamine - Assignment Example

Issues to Consider in Tablet Formulation of a new non-Sedating Antihistamine Insert (s) Issues to Consider in Tablet Formulation of a new non-Sedating Antihistamine Introduction There are a number of issues and factors that should be taken into consideration during the design of a tablet or liquid formulation for a new non sedating antihistamine drug. According to Aulton and Taylor (2013, p.4, chapter 1) a tablet as a pharmaceutical dosage form often contain a mixture of different active substances as well as excipients that will then pressed and compacted into a solid dose. On the other hand, the tablet for the new drug should also be formulated in such a way that it delivers an accurate dosage to the specific intended site when administered orally, buccally or sublingually (Patrick, 2009, p.172). Non sedating antihistamines are antihistamine drugs that can not enter brain and cause drowsiness in the patient and are normally used in treating the symptoms of reactions to stings and bites as well as allergies. The drugs work by blocking the activity of histamine produced by the body as part of the natural immunity. Compared to the sedating antihistamines, non sedating antihistamine drugs are generally more designed to be more selective for the peripheral H1 receptors rather than the cholinergic and central nervous system H1 receptors. This selectivity particularly makes the drugs to avoid sedation and other adverse reactions that may result when it is ingested to be used against allergic reactions (Tillement, Timmerman, Frossard and Levander, 2001, p.228). This paper critically discusses the issues that should be considered in the design of a tablet formulation for a non sedating antihistamine drug with a half life of 16 hours and an adult dose of 2mg per day as well as for a children liquid formulation (2-12 years old). 1. Tablet Formulation One of the main factors to consider when formulating the new non sedating antihistamine drug is its disintegration time. This is particularly attributed to the fact that the new drug is expected to have a short half –life of 16 hours. For example, in order to ensure the effectiveness of the drug within its relatively short half-life, the tablet should be formulated in a way that it takes a short time for the tablet to break up into particles or granules once it has been ingested. According to Nelson (2007, p.46), this may be achieved by adding sufficient disintegrants, not using too much binder and avoiding compressing the tablets too hard in order to modify the disintegration and enhance a rapid effect of the drug before it reaches its half life. In addition, another issue related to the tablet formulation of the new non sedating antihistamine that should be considered is its potency. Since an adult dose will only be 2mg per day, the amount of the active drug substance per each tablet should be determined to ensure that it is sufficient for every tablet. Patient Compliance Patient Compliance is another important factor that will play a critical role in the design of a tablet formulation for a new non sedating antihistamine drug. This is because the degree to which the ability of the patients to follow the prescription will impact on the overall effectiveness of the drug. In this regard, the design of the tablet formulation should ensure that medication adherence does not have a serious effect on the effectiveness of the new drug tablets. This is critically important in developing sufficient potency of the drug. Pharmaceutics The pharmaceutics of the new non sedating antihistamine drug generally refers to the relationship between the drug and its route of administration as well as hot it enters the systemic circulation. The information on the pharmaceutics of the drug may be used to help better control the safety of the drug and minimize its potential side effects. Pharmacokinetics and Physiochemical Properties  The pharmacokinetics and physiochemical properties of the drug have an important effect on the new drugs pharmacological effect on the body of the patients and can effectively be used to determine the appropriate drug dosage regimens, drug concentration and time profiles. According to Aulton and Taylor (2013, p.292), Pharmacokinetics is the characterization and study of a drugs course of absorption, distribution, metabolism and finally its elimination. Some of the major properties that should be taken into consideration include the drugs half life, its distribution volume, peak plasma concentration, infusion rate bioviability, proportion that reaches the site of action and the drug’s elimination rate. For example, the plasma concentration of non sedative drugs normally interact is often raised by certain drugs and this information can help avoid co-administration of the new drug with such drugs (Desager and Horsmans, 1995, p.420). Excipients Excipients are either natural or synthetic chemical substances formulated alongside active medication ingredients. Pharmaceuticals inactive ingredients or excipients are often essential to a drug product’s performance. For the tablet formulation, the required excipients for the new non-sedating antihistamine tablet includes binders, coloring pigment, lubricants and disintegrants as shown in the figure below. Fig 1: Summary of the Tablet formulation excipients and their functions Excipients Function Methyl cellulose, gelatin, sucrose, lactose, xylitol, cross-linked PVP, Microcrystalline cellulose, (Binders) (Aulton and Taylor, 2013, p.548) Required for holding the ingredients of the ingredients of the tablet together while at the same time giving volume to low active dose drug tablets like the new non sedative antihistamine drug being formulated (Aulton and Taylor, 2013, p.548, Chapter 5). This is important in ensuring the stability of the drug since anti-histamine drugs normally contain a number of additives. Gelatin, shellac, hydroxypropyl methylcellulose (Tablet Coating) Protect the ingredients of the tablet from being affected by moisture or air as well as control the rate of drug release. The tablet will also be coated to prevent its potential degradation by the acidic environment of the stomach since the active ingredients of most non sedative antihistamines are highly affected by low pH. Coloring pigment Used to make the tablet attractive magnesium stearate (Lubricants) Enhances tabletting efficiency Croscarmellose sodium, sodium starch glycolate (Disintegrants) Promote the breaking up of the tablet once it has been ingested into the digestive track. The diintegrants are particularly important in enhancing faster the breaking up and absorption since it has a short half life of 16 hours. Magnesium carbonate, Colloidal SiO2(Glidants) Reduce interparticulate friction thereby improving the flowability of the drug. This is important since there are a number of additives used in the formation of the non sedative antihistamine some of which may have strong interparticulate friction. Stability The stability of the drug is the ability of its pharmaceutical dosage form to effectively maintain its chemical, physical and therapeutic properties during storage and usage. The formulation of the tablet compound should ensure an easy disaggregation, disintegration and dissolution of the drug in the stomach, intestines and bloodstream. According to Qiu, Chen, Zhang, Liu and Porter (2013, p.20), it is essentially critical that the solute and the solvent of the drug remain chemically and physically stable during the storage of the drug. In this regard, fast dissolving tablets must always be prepared by a direct compression method. However, a fully designed tablet must be optimized to increase their solubility nature to the body system. The main types of disintegration that may affect the stability of tablet drugs include chemical degradation, physical degradation and microbial degradation (Qiu, Chen, Zhang, Liu and Porter (2013, p.87). Fig 2: Types of Disintegration and their Prevention Type of Disintegration Cause Prevention Chemical degradation Moisture, heat, light, oxygen/air, pH. Coating the tablet, use of stabilizers Physical degradation physical instability of the tablet Use of stabilizers, binders and coating Microbial degradation Microbial contamination Coating Dissolution Dissolution is one of the most important stages of drugs administered in solid forms such as tablets and capsules since they need to dissolve and form solutions in the gastrointestinal tract before they can be ingested into the body (Aulton and Taylor, 2013, p.2, Chapter 1). According to Aulton and Taylor (2013, p.14, Chapter 1), a drug’s rate of dissolution can be affected by unsuitable choice of the formulation additives and excipients used. Some of the factors that may affect the dissolution rate of the new drug and should therefore be taken into consideration include the level of tablet compression, tablet granule size and the amount of binders such as starch used. 2. Liquid Formulation Just like the tablet formulation, the liquid formulation of the new non sedating antihistamine drug will also combine a number of compounds including stabilizers, solubilizers, excipients, builking agents, buffers and viscosity enhancers among others. Dissolution property of the new drug would be particularly important since the formulation for children would be in liquid form. On the other hand, since many of the common active ingredients of non sedative antihistamines as well as some of the excipients have unpleasant tastes, there is a need to include flavors and sweeteners like Sucrose, dextrose to improve its taste and make it more acceptable to children. Solutions When designing the liquid formulation for a new non sedating antihistamine drug, solutions is preferable over suspension because it provides a more homogenous mixture which will enhance accurate dosing. Although water is the most commonly used solvent, the other solvents like glycerin should be considered since the active ingredients or some of the excipients may not be soluble in water. Stability Stability is another critical issue that should be put into consideration during the formulation of the liquid non sedative antihistamine drug. For example, the drug is likely going to face the problems of faster degradation since liquid formulations are normally less stable overtime as compared to the solid ones. Excipients The excipients that will be required for the liquid formulation include solubilizers to facilitate the solubility of the drug, stabilizers .Excipients ensure a perfect handling of active substance for liquid formulation such as by aiding in vitro stability thus preventing denaturation. Fig 3: Excipients for the liquid formulation and their functions Excipients Function Sorbitol or dextrose (Solubilizers) Increases the bioavailability of the drug Microcrystalline cellulose, Lactose(diluents) Provide bulk and help in the dosing of potent ingredients (Patrick, 2009, p.78). This is important since the active ingredient of non sedative antihistamine drugs normally form a small component of the entire liquid formulation. Sucrose, dextrose or Aspartame (Flavors) Sweeten the drug and masks the unpleasant taste of active ingredients of the non sedative anti histamine drug. This is particularly important since it is meant for children aged between 2 and 12 Sucrose(Viscosity enhancers) Enhances the flow of the drug liquid formulation Conclusion In conclusion, the design of a tablet or liquid formulation for a new non sedating antihistamine drug involves a diverse number of factors that should be taken into consideration in order to come with a viable and effective pharmaceutical dosage form. Generally, apart from the active ingredients, the new drug must also include a mixture of excipients some of which include binders, coloring pigment, lubricants and disintegrants, flavors and diluents among others. References Aulton, M.E. & Taylor, K.M. 2013. Aultons Pharmaceutics: The Design and Manufacture of Medicines.4th edition. Edinburgh: Churchill Livingstone. Available at Nelson, W.L. 2007. Antihistamines and Related Antiallergic and Antiulcer Agents. Hagerstown, Maryland: Lippincott Williams & Wilkins.. Desager, J., Horsmans, Y. 1995. Pharmacokinetic-pharmacodynamic relationships of H1 antihistamines. Clin Pharmacokinet, 28(2),pp. 419–432. Patrick, G. 2009. An Introduction to Medicinal Chemistry. 4th ed. New York: Oxford University Press. Qiu, Y., Chen, Y., Zhang, G. Liu, L. & Porter. W. 2013. Developing Solid Oral Dosage Forms: Pharmaceutical Theory and Practice. New York: Academic Press. Available at Simons, F. Estelle, R. 2004. Advances in H1-antihistamines. The New England Journal of Medicine 351(21), pp. 2203-2217. Walsh, G.M, Tillement, J.P., Timmerman, H., Frossard, N. & Levander, S. 2001. New insights into the second generation antihistamines. Drugs 61(2), pp. 207-236. Read More