Development And Characterization of Lornoxicam Tablets Incorporating Banana Starch as A Superdisintegrating for Enhanced Dissolution

Abstract

Orally disintegrating tablets (ODTs) are an emerging trend in novel drug delivery system and have received ever-increasing demand during the last few decades. ODTs are solid unit dosage forms, which disintegrate or dissolve rapidly in the mouth without chewing and water. This type of property in dosage form can be attained by addition of different excipients, in which disintegrants are the key adjuvant. In recent years, several newer agents have been developed known as super-disintegrants. Super-disintegrants are used to improve the efficacy of solid dosage form and influence the release rate of dosage form. Diverse categories of super- disintegrants are such as synthetic, semi-synthetic, natural, and co-processed blends. These have been employed to develop effectual ODTs and to overcome the limitations of conventional tablet dosage forms. The plant-derived natural super disintegrants comply with many requirements of pharmaceutical excipients as they are non-toxic, stable, easily available, associated with less regulatory issues as compared to their synthetic counterpart, and inexpensive; also these can be easily modified into more polar form. This review discusses about the development of various kinds of natural super-disintegrating agents, along with their role in the tablet disintegration and as potent candidate to be used in ODTs, which are being used in the formulation to provide the safer, effective drug delivery with patient compliance.

Keywords

Banana Starch, Orodispersible tablet, lornoxicam tablet, superdisintegrant, disintegration.

Introduction

The tablet is the most widely used dosage form because of its convenience in terms of self administration,compactness and ease in manufacturing. However, geriatric and pediatric patients experience difficulty in swallowing conventional tablets, which leads to poor patient compliance. To overcome this weakness, scientists have developed innovative drug delivery systems known as mouth dissolving tablets. Their characteristic advantages such as administration without water, anywhere, anytime lead to their suitability to geriatric and pediatric patients. They are also suitable for the mentally ill, the bedridden and patients who do not have easy access to water. The benefits, in terms of patient compliance, rapid onset of action, increased bioavailability and good stability made these tablets popular as a dosage form in the current market. Drug delivery through oral route is the most common and preferred route of drug administration both for solid and liquid dosage forms. However solid dosage forms are popular because of ease of administration, precise dosage, self medication, pain avoidance and most importantly the patient compliance1. The International Pharmaceutical Excipients Council (IPEC) defines an excipient as any substance other than the active drug or prodrug that is included in the manufacturing process or is contained in the finished pharmaceutical dosage form. The reasons for their use are several. In the preparation of a tablet, from a drug into dosage form, pharmaceutical excipients are required. Fillers are added to increase the bulk of the formulation, and lubricants to reduce friction during the tableting process. Disintegrants are one of the essential excipients added to tablet formulations to enhance the breakup of the tablet into smaller fragments in aqueous environment thereby facilitating and promoting more rapid release of the drug substances . They usually promote moisture penetration and dispersion of the tablet matrix to facilitate tablet disintegration which is frequently a prerequisite for dissolution and release of the active drug from the tablet. Starch is one of the multifunctional excipient used in tablet formulations as disintegrant.

Natural Superdisintegrants: These superdisintegrating agents are natural in origin and are preferred over synthetic substances because they are comparatively cheaper, abundantly available, non-irritating and nontoxic in nature. The natural materials like gums and mucilages have been extensively used in the field of drug delivery for their easy availability, cost effectiveness, Eco friendliness, emollient and non-irritant nature, non - toxicity, capable of multitude of chemical modifications, potentially degradable and compatible due to natural origin. There are several gums and mucilages are available which have super-disintegratingactivity.

Starch: Starch is the most abundant carbohydrate reserve in plants and is found in leaves, flowers, fruits, seeds, different types of stems and roots. Starch is used by plants as source of carbon and energy . The biochemical chain responsible for starch synthesis involves glucose molecules produced in plant cells by photosynthesis. Starch is formed in the chloroplasts of green leaves and amyloplasts, organelles responsible for the starch reserve synthesis of cereals and tubers . Starch production in the chloroplast is diurnal and performed rapidly by the plant. Conversely, starch reserves produced by amyloplasts are deposited over several days, or even weeks. Starch is stored and cyclically mobilized during seed germination, fruit maturation and the sprouting of tubers . The main location of starch synthesis and storage in cereals is the endosperm. Major starch sources are cereals (40 to 90%), roots (30 to 70%), tubers (65 to 85%), legumes (25 to 50%) and some immature fruits like bananas or mangos, which contain approximately 70% of starch by dry weight . The accumulation pattern of starch granules in each plant tissue, shape, size, structure and composition is unique to each botanical species.

Lornoxicam : Lornoxicam, also known as chlortenoxicam, is a nonsteroidal anti-inflammatory drug (NSAID) of the oxicam class with analgesic (pain relieving), anti-inflammatory and antipyretic (fever reducing) properties. It is available in oral and parenteral formulations. It was patented in 1977 and approved for medical use in 1997.Brand names include Xefo and Xefocam among others.

Medical Uses : Lornoxicam is used for the treatment of various types of pain, especially resulting from inflammatory diseases of the joints, osteoarthritis, surgery, sciatica, and other inflammations.

Contraindications : The drug is contraindicated in patients who must not take other NSAIDs, possible reasons including salicylate sensitivity, gastrointestinal bleeding and bleeding disorders, and severe impairment of heart, liver or kidney function. Lornoxicam is not recommended during pregnancy and breastfeeding and is contraindicated during the last third of pregnancy.

Interactions : Interactions with other drugs are typical of NSAIDs. Combination with vitamin K antagonists like warfarin increases the risk of bleeding. Combination with ciclosporin can lead to reduced kidney function, and to acute kidney injury in rare cases. Lornoxicam can also increase the adverse effects of lithium, methotrexate and digoxin and its derivatives. The effect of diuretics, ACE inhibitors and angiotensin II receptor antagonists can be reduced, but this is only relevant in patients with special risks like heart failure. As with piroxicam, cimetidine can increase plasma levels but is unlikely to cause relevant interactions.

Structure Of Lornoxicam :

IUPAC Name : 6-chloro-4-hydroxy-2-methyl-1,1-dioxo-N-(3,4,5,6- tetradeuteriopyridin-2-yl)thieno[2,3-e]thiazine-3- carboxamide

Formula :   C13H10ClN3O4S2

Molecular Weight : 371.81 g·mol−1

Category : NSAIDs

Use : to reduce and relieve pain and inflammation (swelling) in osteoarthritis and rheumatoid arthritis.

BCS Class : Class II

Banana Starch : Banana is a tropical fruit crop that is consumed at large, not only because of the quantity produced but also because it serves the calorific needs of millions of people. Banana is a potential source of high starch content (more than 60%). The application of starch for various purposes is dependent upon its structural, physicochemical, and functional properties. A native starch does not possess all required properties for specific use in the food product. To improve its application, starch can be modified physically, chemically, and enzymatically. Each of these modification methods provides different characteristics to the modified starch.

Evaluation of powder blend (precompression parameters)

The powder mix was evaluated for various flow properties such as angle of repose, bulk and tapped density, Hausner’s ratio, and Carr’s index.

Angle of repose :

The angle of repose of powder was carried out using the fixed funnel method. The accurately weighed quantity of powder mix was taken in a funnel.The height of the funnel was maintained in such a way that the tip of the funnel just touched the apex of the heap of the powder. The powder was allowed to flow through the funnel without any resistance on to the surface.The diameter  and height of the powder cone was measured.The angle of repose was determined using the following equation:

tan =h/r,

where h and r are the height and radius of the powder cone, respectively.

Hausner ratio:

The Hausner ratio is also used in industries as an indication of the flowability of a powder. It is calculated by the formula

H = ρT/ρB

Where ρB is the freely settled bulk density of the powder, and ρT is the tapped bulk density of the powder. The Hausner ratio is not an absolute property of a material; its value can vary depending on the methodology used to determine it. Use of these measures persists however, because the equipment required to perform the analysis is relatively cheap and the technique is easy to learn.

Carr’s index:

The Carr index is frequently used in pharmaceutics as an indication of the flowability of a powder. A Carr index greater than 25 is considered to be an indication of poor flowability and Parashar et al., American Journal of PharmTech Research. 2012; 2(1) ISSN: 2249-3387www.ajptr.com 72 below 15 of good flowability. The Carr index is an indication of the compressibility of a powder. It is calculated by the formula

C = 100 VB-VT/ VB

Where VB is the freely settled volume of a given mass of powder, and VT is the tapped volume of the same mass of powder. It can also be expressed as

C = 100× (1 -ρB/ρT)

Where ρB is the freely settled bulk density of the powder, and ρT is the tapped bulk density of the powder.

Evaluation Of Tablet :

Tablet Hardness : The tablet was placed between the two arms of the Vernier caliper, and thickness was determined. Five measurement  were taken.

Weight Variation : Twenty tablets were selected arbitrarily from each formulation and weighed individually using a digital balance (Shimadzu Corporation, Japan; Model No. BL 220H). The individual weights were noted and compared with the average weight for the weight variation

Friability : Twenty tablets were weighed and then placed in a plastic chambered friabilator USP type Roche friabilator attached to a motor revolving at a speed of 25 rpm for 4minutes. The tablets were reweighed, and the percentage weight loss (friability) was calculated using the following formula:

Friability = [(Initialweight − Finalweight)/(Initialweight)] × 100%.

Thickness : Thickness of tablet was determined by using vernier calliper.

Dissolution Test : Dissolution testing is used to measure the release rate of an active component from a solid dosage form under controlled conditions. This technique is used to assess the performance of tablets, capsules, films and other solids. Dissolution testing is useful in guiding the formulation development procedure and comparing finished products with different commercial preparation.Another application of dissolution testing is assessing the quality of a sample by determining the release of active pharmaceutical ingredient from the formulation is within acceptable limits.

Disintegration Test : The disintegration test is a measure of the time required under a given set of conditions for a group of tablets to disintegrate into particles which will pass through a 10 mesh screen. For a drug to be absorbed from a solid dosage form after oral administration, it must first be in solution, and the first important step toward this condition is usually the break-up of the tablet; a process known as disintegration.

Uniformity of weight: 20 Tablets of all the batches were collected randomly during compression and weight of individual tablet was carried out. Limit: Weight of all individual tablets should be in the limit of Average wt ± 7.5%. Average weight was carried out by calculating the total wt. of 20 tablets (individually weighed) and dividing this value by 20.

Oral Route : The oral route is the most preferred route for systemic and local drug delivery. However, the oral drug delivery system faces the harsh physiological and physicochemical environment of the gastrointestinal tract, which limits the bioavailability and targeted design of oral drug delivery system.

Tablets : Tablets may be defined as solid pharmaceutical dosage forms containing medicament or medicaments with or without suitable excipients & prepared either by compression or moulding.

ADVANTAGES OF TABLET

Some of the potential advantages of tablets are as follows.

1. They are the unit dosage form having greatest capabilities amongst all the oral dosage form for the dose precision and least content variability.

2. Their cost is lowest amongst all the oral dosage forms.

3. They are the lightest and the most compact amongst all the oral dosage form.

4. They are easiest and cheapest for packaging and transportation.

CLASSIFICATION OF TABLETS

Based on the route of administration or the function, the tablets are classified as follows.

1) Tablets ingested orally.

a) Compressed tablet

b) Multiple compressed tablet

i) Layered Tablet

ii) Compression coated Tablet

c) Repeat action Tablet

d) Delayed action and enteric coated Tablet

e) Sugar and chocolate coated tablet

f) Film coated tablet

g) Chewable Tablet

2) Tablets used in the oral cavity.

a) Buccal Tablet

b) Sublingual Tablet

c) Troches and Lozenges

d) Dental cones

3) Tablets administered by other routes.

a) Implantation Tablet

b) Vaginal Tablets

4) Tablets used to prepare solution.

a) Effervescent Tablet

b) Dispensing Tablet

c) Hypodermic Tablet

d) Tablets Triturates

TABLET MANUFACTURING METHODS

Tablets are manufactured by wet granulation, Dry granulation or direct compression method as :

1] Wet Granulation

Wet granulation is the process in which a liquid is added to a powder in a vessel equipped with any type of agitation that will produce agglomeration or granules.These granules after drying are compressed to form tablets.

2] Dry Granulation

In this technique, there is no use of liquids. The process involves the formation of slugs. Then the slugs are screened or milled to produce granules. The granules formed are then compressed to form tablets.

3) Direct compression

The term direct compression is used to define the process by which tablets are compressed directly from powder blends of active ingredient and suitable excipients, which will flow uniformly in the die cavity & forms a firm compact.

Composition :

Ingredients	Role
Lornoxicam	Antiinflammatory
Microcrystalline cellulose	Binder
Banana starch	Disintegrating agent
Sucrose	Sweetner
Lemon Flavour	Flavouring agent
Talc	Lubricant
Magnesium stearate	Stabilizer

CONCLUSION :

The results obtained indicate that the physicochemical and material tablet properties of the banana starch varied considerably. When used as disintegrant in lornoxicam tablet formulations, banana starch had longer disintegration times in the lornoxicam  tablets banana starch disintegrants. The results showed that banana starch possesses acceptable disintegranting characteristics   in lornoxicam tablet formulation.

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