INTRODUCTION:

Recent advances in novel drug delivery (NDDS) aims to enhance safety and efficacy of drug molecule by formulating a convenient dosage form for ease of administration and to achieve better patient compliance.

The tablet is the most widely used dosage form because of its convenience in terms of self-administration; accurate dosage and pain avoidance. But there are certain problems with conventional tablets dosage forms like difficulty to swallow. Dysphagia or difficulty in swallowing is seen to afflict nearly 35% of the general population. It can be due to:

1. Hand tremors in elders.

2. In young individuals because of their under developed muscular and nervous systems.

3. Mentally ill or mentally disabled.

4. Uncooperative patient.

5. Some cases such as motion sickness, sudden episode of allergic attack or coughing.

6. Unavailability of water.

Number of pathological conditions including Stroke, Parkinson's disease, AIDS other neurological disorders including cerebral palsy.

For this reason, tablets that can rapidly dissolve or disintegrate in the oral cavity have attracted a great deal of attention.

Fast dissolving tablet is the tablets which dissolve/disintegrate rapidly in the oral cavity resulting in solution or suspension without the need of water. This type of tablet dissolves in the saliva within <60 sec.

FDT differ from traditional tablets that they are designed to be dissolve on the tongue rather than swallowing whole. When FDT put on the tongue, it disintegrates instantaneously releasing. In another words a fast-dissolving drug delivery system, in most cases, is a tablet that dissolves or disintegrates in the oral cavity without the need for water or chewing the drug which dissolve or disperse in saliva.

A fast-disintegrating drug delivery system, in most cases, is a tablet that dissolves or disintegrates in the oral cavity without the need of water or chewing. Most fast-disintegrating delivery system films must include substances to mask the taste of the active ingredient. This masked active ingredient is then swallowed by the patient's saliva along with the soluble and insoluble excipient.

Recent advances in novel drug delivery system aims to enhance safety and efficacy of drug molecule by formulating a convenient dosage form for administration and to achieve patient compliance. Most of the time inconvenience of administration results in high incidence of noncompliance and ineffective drug therapy. Among the dosage forms developed to facilitate ease of medication, rapid disintegrating tablet is one that disintegrates quickly i.e. within 60 sec, in the saliva. As RDT has good taste, color, and flavor, it has good patient acceptability.

Meloxicamis a non-steroidal anti-inflammatory drug (NSAID) used in the treatment of osteoarthritis, rheumatoid arthritis, and painful menstruation and menstrual symptoms. It is a selective cyclooxygenase-2 inhibitor. Meloxicamis a sulfonamide derivative and non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory, analgesic, and antipyretic activities. Meloxicam selectively binds to and inhibits cyclooxygenase (COX)-2, thereby preventing the conversion of arachidonic acid into prostaglandins, which are involved in the regulation of pain, inflammation, and fever. This NSAID does not inhibit COX-1 at therapeutic concentrations and therefore does not interfere with blood coagulation. There fore in the present investigation attempt has been made to improve the performance of drug for both the conditions by modifying dosage form.

Meloxicam is an orally bioavailable oxicam and non-steroidal anti-inflammatory drug (NSAID), with analgesic, anti-pyretic, anti-thrombotic and anti-inflammatory activities. Upon oral administration, Meloxicambinds to and inhibits the activity of the cyclooxygenase enzymes (COX) type 1 (COX-1) and type 2 (COX-2). This blocks COX-mediated signaling pathways, which leads to reduced prostaglandin and thromboxane production and decreased pain, fever and inflammation. Meloxicamis a phenothiazine-derived monocarboxylic acid amide obtained by formal condensation of the Carboxy group of 6-chloro-4-hydroxy-2-methylthieno [2,3-e] [1,2] thiazine-3-carboxylic acid 1, 1-dioxide with the amino group of 2-aminopyridine. Used for the treatment of pain, primarily resulting from inflammatory diseases of the joints, osteoarthritis, surgery, sciatica and other inflammations. It has a role as a non-steroidal anti-inflammatory drug, a non-narcotic analgesic and an antipyretic. It is a thienothiazine, a member of pyridines, a monocarboxylic acid amide, an organ chlorine compound and a heteroarylhydroxyl compound.

MATERIALS AND METHODS:

Materials:

Meloxicam were obtained as a gift sample from Glenmark generics Ltd, Mumbai, India. Menthol, Magnesium stearate, Aspartame and Mannitol were purchased from local authorized dealer.

Formulation of Mouth Dissolving Tablets of Meloxicam:

The FDTs tablets of Meloxicam were prepared using the subliming agent, menthol and KYRON T-314 as superdisintegrant, Mannitol as diluent, Mannitol as sweetening agent, alcoholic solution of polyvinyl Pyrrolidone (PVP K-30) as binder, Aerosil as flow promoter and magnesium stearate as lubricant, the composition of each batch is shown in Table 1.

Table 1: Composition of Different Batches of Mouth Dissolving Tablets of Meloxicam

Ingredients	QUANTITIES (mg)
Ingredients	F1	F2	F3	F4	F5
Meloxicam	8	8	8	8	8
Menthol	20	20	25	25	25
Kyron T-314	20	20	20	25	25
Mannitol	145	145	135	130	130
PVP-K30	7	7	7	7	7
Aerosil	3	3	3	3	3
Mg Sterate	2	2	2	2	2

METHODOLOGY:

The raw materials were passed through a 100-mesh screen prior to mixing. The drug and other ingredients were mixed together and a sufficient quantity of alcoholic solution of PVP K-30 (10% w/v) was added and mixed to form a coherent mass. The wet mass was granulated using sieve no. 12 and regranulated after drying through sieve no. 16. Granules of the all formulations were then dried in a vacuum oven (Vertex, VT4810) at 60°C for 12 h resulting in localized drying. The final moisture content of the granules was found to be between 1-2%, which was determined using an IR moisture balance. During drying, the menthol sublimed with the formation of a porous structure on the surface of the tablet. The dried granules were then blended with talc, magnesium stearate and compressed into tablets using flat face round tooling on a Rimek-I rotary tablet machine (KarnavatiEngg. Pvt. Ltd, Ahmedabad). Sublimation was performed from tablets instead of granules at 600°C in selected batch (F5).

Evaluation of Formulated Tablets:

Micromeretics (pre-compression parameters):

Angle of Repose (Marshall, 1987):

Angle of repose was determined using fixed funnel method. The blend was poured through a funnel that can be raised vertically until a maximum cone height (h) was obtained. Radius of the heap (r) was measured and the angle of repose (ө) was calculated using the formula.

θ = tan -1 (h / r)

Bulk Density (Marshall, 1987):

Bulk density was determined by pouring the blend into a graduated cylinder. The bulk volume (V) and weight of the powder (M) was determined. The bulk density was calculated by using the below mentioned formula,

Mass of Granules

Bulk density = -----------------------------

Volume

Tapped Density (Marshall, 1987):

The measuring cylinder containing a known mass of blend was tapped for a fixed time. The minimum volume (Vt) occupied in the cylinder and the weight (M) of the blend was measured. The tapped density was calculated using the following formula

Weight of Blend

Tapped density = ------------------------------------

Volume occupied in cylinder

Compressibility Index (Lindberg et al., 2004):

The simplest way for measurement of free flow of powder is compressibility, a indication of the ease with which a material can be induced to flow is given by compressibility index (I) which is calculated as follows,

Vo-Vt

I = ---------------

Vbx

Here,

Vo is bulk volume and Vt is tapped volume. The value below 15% indicates a powder with usually give rise to good flow characteristics, whereas above 25% indicate poor flow ability.

Hausner’s Ratio (Lindberg et al., 2004):

Hausner’s ratio is an indirect index of ease of powder flow. It is calculated by the following formula,

Tapped density

Hausner ratio = ----------------------------

Bulk density

Lower Hausner’s ratio (<1.25) indicates better flow properties than higher ones (>1.25).

Thickness:

Thickness of tablet was determined by using verniercalliper (Mitutoya, Model CD-6 CS, Japan).

Hardness (Marshall, 1987):

The crushing strength of the tablets was measured using a Monsanto hardness tester (Sheetal Scientific Industries, Mumbai, India). Three tablets from each formulation batch were tested randomly and the average reading noted.

Friability (Marshall, 1987):

Twenty tablets were weighed and placed in a Roche Friabilator (Electrolab, India). Twenty reweighed tablets were rotated at 25 rpm for 4 min. The tablets were then dedusted and reweighed and the percentage of weight loss was calculated. The percentage friability of the tablets were measured as per the following formula,

Initial weight – Final weight

Percentage friability = ---------------------------------X 100

Initial weight

Weight Variation (Marshall, 1987):

Randomly, twenty tablets were selected after compression and the mean weight was determined. None of the tablets deviated from the average weight by more than ±7.5% (USPXX).

Wetting Time (Yunxia, 1996):

A piece of circular tissue paper (8cm) folded twice was placed in a Petri dish (Internal Diameter=9cm) containing 10 ml of buffer solution simulating saliva pH 6.8. A tablet was placed on the paper and the time taken for complete wetting was noted. Three tablets from each formulation were randomly selected and the average wetting time was noted. The results are tabulated.

In Vitro Dispersion Time (Kimura et al., 1992):

In vitro dispersion time of prepared tablet was done by dropping the tablet in 10 ml measuring cylinder containing 6 ml of simulated salivary fluid (pH 6.8). Time required for complete dispersion of tablet was measured.

Dissolution Study:

In vitro release of Meloxicam from tablets was monitored by using 900ml of simulated intestinal fluid, SIF (USP phosphate buffer solution, pH 7.4) at 37±0.5°C and 50rpm using programmable dissolution tester [Paddle type, model TDT-08L, Electro lab, (USP), India]. 5ml Aliquots were withdrawn at one minute time intervals and were replenished immediately with the same volume of fresh buffer medium. Aliquots, following suitable dilutions, were assayed spectrophotometrically (UV-1700, Shimadzu, Japan) at 378nm.

RESULTS AND DISCUSSION:

Five formulations of Meloxicam were prepared with different concentration of Kyron T-314 and PVP K30, for each formulation, blend of drug and excipients were prepared and evaluated for various parameters as explained earlier. The powder blend was compressed using direct compression technique. Bulk density was found in the range of 0.52 – 0.59g/cm3 and the tapped density between 0.66 - 0.69g/cm3. By using these two-density data, Hausner’s ratio and compressibility index was calculated and the compressibility correlation data indicated a fairly good flowability of the powder blend. The good flowability of the powder blend was also evidenced with angle of repose (range of 24.35-27.54º), which is below 40º indicating good flowability (Table 2). Tablet thickness varies between 3.4±0.06 - 3.6±0.05 the prepared tablets possess good mechanical strength and sufficient hardness in the range of 2.9±0.51 - 3.6±0.10, friability values below % indicates good mechanical resistance of tablet, all formulations passed weight variation test and the percentage drug content of tablets were found to be between 86.81±1.2 - 97.25± 1.3 and the in-vitro drug release from F5 formulation indicated faster and maximum release (Table 3).

Table 2: Micromeretics of Meloxicam Blend

Formulation Code	Bulk density (gm/ml)	Tapped density (gm/ml)	Angle of repose (θ)	Percentage compressibility	Hausner’s Ratio
F 1	0.55	0.66	25.55	15.05	1.19
F 2	0.52	0.68	24.35	15098	1.27
F 3	0.57	0.69	25.23	14.57	1.23
F 4	0.59	0.67	27.54	15.47	1.21
F 5	0.59	0.66	26.77	14.78	1.32

Table 3: Characterization of prepared and Marketed Meloxicam Tablets.

Parameters	F1	F2	F3	F4	F5	Marketed Tablet
Hardness (kg/cm2)	3.1±0.30	3.4±0.68	2.9±0.51	3.1±0.63	3.6±0.10	3.2±0.20
Friability (%)	0.743± 0.04	0.629± 0.06	0.637± 0.05	0.688±0.04	0.574±0.04	0.643± 0.03
Weight variation (mg)	204±3	199±2	203±3	197±1	200±1	201±3
Thickness (mm)	3.5±0.03	3.4±0.07	3.6±0.05	3.4±0.06	3.5±0.01	3.3±0.04
Wetting time (s)	38.2±2.5	39.3±1.5	43.6±2.2	39.1±2.0	29.4±1.5	34.2±2.6
In-vitro dispersion time (s)	68.3±2	62.1±1	56.2±2	53.7±3	41.8±2	58.3±1
Drug content	99.24± 3.24	98.44± 2.54	98.60±3.04	98.93±1.81	99.42±1.27	96.24± 2.21
Drug release in 5 min (%)	69.03±2	72.17±2	73.72±2.5	75.54±3	78.37±1.	68.03±1
Drug release in 30 min (%)	86.81±1.2	88.11±1.6	88.73±2.5	93.26±2.7	97.25± 1.3	89.81±1.1

CONCLUSION:

Formulation F5 was found to be best among all other formulations, because it has exhibited faster wetting time, good taste and faster disintegration time when compared to all other formulations.

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Received on 10.01.2021 Modified on 26.01.2021

Res. J. Pharma. Dosage Forms and Tech.2021; 13(2):113-117.

DOI: 10.52711/0975-4377.2021.00020