Research & Reviews in Pharmacy and Pharmaceutical Sciences
Menue-ISSN:2320-1215 p-ISSN: 2322-0112
e-ISSN:2320-1215 p-ISSN: 2322-0112
1Department of Pharmaceutics, Cherraan’s College of Pharmacy, Coimbatore, Tamil Nadu, India.
2Department of Pharmaceutics, College of Pharmacy, Sri Ramakrishna Institute of Paramedical Sciences, Coimbatore, Tamil Nadu, India.
Received: 26/08/2014; Revised: 14/09/2014; Accepted: 17/09/2014
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The Combination Therapy of different mechanism of action of drugs plays an important role in the measurement of Type II Diabetes Mellitus. The effect of diabetes develops specific complications of retinopathy, nephropathy, neuropathy, cardiac vascular diseases and cerebro vascular diseases. Combination therapy is beneficial for various diseases over monotherapy. The oral hypoglycemic drug combination therapy is most suitable for chronic disorder. Sulfonyl ureas, Alpha glucosidase inhibitors, Biguanides, Meglitinides and Thiazolidinediones are important in Combination Therapy. Bilayer tablet is suitable for sequential release of two drugs in combination, in which one layer is initial dose as immediate release and second layer is maintenance dose. This article explains the dual therapy of bilayer tablet and combination of anti-diabetic drugs which improves the patient compliance and provides synergistic effect.
Diabetes, Bilayer Tablets, Antidiabetic Drugs, Fixed Dose Combination.
Diabetes is a group of metabolic disease characterized by hyperglycemia resulting from defects in insulin secretion, insulin action or both. [1] Diabetes mellitus mainly classified into two categories, Insulin dependent diabetes mellitus when the pancreas does not produce enough insulin to properly control blood sugar levels, in this condition the patient completelydepends parental formulation of insulin another one Non-insulin dependent diabetes mellitus, the cells of the body become resistant to insulin which are treated with oral antidiabetic agents such as Sulfonylureas, Biguanides, Thiazolidinediones derivatives, carbohydrate analogue and DPP- 4 inhibitors.
The development of diabetes projected to reach pandemic proportion over the next 10-20 years. Diabetes mellitus may present with characteristic symptoms such as thirst, polyuria, blurring of vision, and weight loss.Often Symptoms are not severe, or may be absent, and consequently hyperglycaemia sufficeint to cause pathological and functional changes may be present for a long time before the diagnosis is made. In the presence of marked hyperglycaemia in newly diagnosed symptomatic Type II diabetes (HbA1c > 8%, FPG>11.1 mmol/L, or RPG > 14mmol/L), an oral anti-diabetic agents can be considered at the outset together with lifestyle modification. Globally, the number of diabetes patients has risen sharply. While in 1985, 30 million people had diabetes, the number rose to 150 million in 2000. In 2010, 285 million people (6.6% of the global population in the age group 20-79) were found to be diabetic. However, by 2030, an estimated 435 million people are expected to suffer from this disease 7.8% of the adult population. The burden of diabetes is enormous and escalating at an alarming rate. Nearly 26 million Americans have the disease, including over 10% of the total adult population and over 25% of the population aged 65 years and older. While most of those individuals have Type II diabetes, nearly 1million Americans have Type I diabetes. An additional 79 million American adults have prediabetes, when added to those with diabetes, suggests that nearly half of the adult population currently has impaired glucose metabolism. Diabetes will cost the world economy near $376 billion in 2010 or 11.6% of total world healthcare expenditure. Though India will spend only 1% of the total diabetes spending worldwide, the amount itself is staggering $2.8 billion. US, on the other hand, will account for $198 billion or 52.7% of the total diabetes spending worldwide. By 2030, diabetes is expected to cost the world economy $490 billion. [2]
The bilayer tablet is usually introduced to improve patient compliance, eliminate frequent dosing and fluctuation in plasma drug concentrations. The dual therapy mainly used to achieve the rapid and extended release of drugs from the formulation. The rapid or immediate release layer containing the loading dose provides a rapid rise of drug concentration. The second layer provides the maintenance dose and prevents the fluctuations of therapeutic concentration of the drug in the body. Various approaches for bilayer tablets. [6]
• Multilayered Tablets – two or three component system
• Compression Coated Tablets – tablet within a tablet coated partially surrounding the core
• Inlay Tablets
• Improve the patient compliance
• Economic
• Synergistic Effect
• Maintain Physical & Chemical Stability
• Retain potency and ensure dose accuracy
• Labour cost is high
• Layer separation
• Cross contamination between the layers
• Single sided tablet press
• Double sided tablet press
• Bilayer tablet with displacement monitoring
Depending upon the condition of the patient, some factors to be taken into account for the treatment
• Degree of hyperglycemia
• Properties of Antihyperglycemic drugs
• Co-Morbidity condition. Management of Diabetes Mellitus can be classified into mainly two a) Oral medicines b) Combination medicine [6,7]
• Oral Monotherapy drugs and the Mechanism of Action (MOA) was discussed in the Table No. 1
Table 1
Fixed dose combination therapy (FDC) is called as a combination of two or more actives in a fixed ratio of doses. The International Diabetic Federation (IDA) and American Diabetic Federation (FDA) tend to suggest if the monotherapy fails along with lifestyle modification the patient should followed by combination therapy. Combination therapy based on the rationale of a multi targeted approach and it helps to achieve and maintain the desired therapeutic targets. The advantages of Fixed Dose Combination are easy of administration, convenience, synergistic effect, complementary mechanism of action, with low dose less side effects, economical, reduce the pill burdenand thereby, improve adherence to treatment, improve tight glycemic control, decrease the incidence/severity of Adverse Drug Reactions, delay the need for insulin therapy.
Previously various works have been done with the combination of diabetes drugs in bilayer tablets which are shown in the Table No. 2 [3,4,5] and Table No.3.
Table 2: Combination of Diabetes Drugs in Bilayer Tablets
Table 3: Marketed available Combination medicines for Diabetes mellitus [6]
Currently Fixed Dose Combination (FDC) of diabetic drugs are fabricated for various reasons which are discussed in the Table No.4.
Table 4: List of Current Fixed Dose Combinations(FDCS) [9]
Fixed Dose Combination therapy of oral hypoglycemic drugs is more suitable for Type II Diabetes mellitus. Bilayer tablets are single pharmaceutical dosage form provides synergistic action, therapeutic justification and reduce the capital investment. Bilayer tablet is quality and GMP requirements can vary widely.