INTRODUCTION:

The oral route is the most popular route used for administration of drugs, which is due in part to the ease of administration and to the fact that gastrointestinal physiology offers more flexibility in dosage form design than most other routes. The terms Sustained release, prolonged release, modified release, extended release or depot formulations are used to identify drug delivery systems that are designed to achieve or extend therapeutic effect by continuously releasing medication over an extended period of time after administration of a single dose.^1,2

There are several reasons for attractiveness of these dosage forms: provides increased bioavailability of drug product, reduction in the frequency of administration to prolong duration of effective blood levels, reduces the fluctuation of peak trough concentration and side effects and possibly improves the specific distribution of the drug. If one were to develop an ideal drugdelivery system, two pre-requisites would be required: Firstly single dose for the duration of treatment whether for days or weeks as with infection, diabetes orhypertension. Second it should deliver the active entity directly to the site of action minimizing the side effects.

There are certain considerations for the preparation of extended release formulations: If the active compound has a long half-life, it is sustained on its own, If the pharmacological activity of the active is not directly related to its blood levels, If the absorption of the drug involves an active transport and If the active compound has very short half-life then it would require a large amount of drug to maintain a prolonged effective dose. The above factors need serious review prior to design.³

Extended release formulations make the drug available over extended time period after oral administration. The extended release product will optimize therapeutic effect and safety of a drug at the same time improving the patient convenience and compliance. By incorporating the dose for 24 hrs into one tablet/capsule from which the drug is released slowly. This formulation helps to avoid the side effects associated with low and high concentrations. The ideal drug delivery system should show a constant zero-order release rate and maintain the constant plasma concentrations.

It is desirable to maintain a therapeutic blood concentration in order to achieve the desirable pharmacological effects. To maintain a narrow range of therapeutic blood concentration it is desirable to have a dosage form that can deliver the drug in a more sustainable or controlled way to achieve the desired results. Extended release tablets and capsules are commonly taken once or twice daily, compared with counterpart conventional forms that may have to be taken three or four times daily to achieve the same therapeutic effect. Typically, extended release products provide an immediate release of drugs that promptly produces the desired therapeutic effect, followed by gradual release of additional amount of drugs to maintain this effect over a predetermined period. The sustained plasma drug levels provided by extended release products often eliminate the need for night dosing, which benefits not only the patient but the patient but the caregiver as well.₄

Drawbacks of Conventional Dosage Form⁵:

· Poor patient compliance, increased chances of missing the dose of a drug with short halflife for which frequent administration is necessary.

· The unavoidable fluctuations of drug concentration may lead to under medication or over medication.

· A typical peak-valley plasma concentration time profile is obtained which makes attainment of steady-state condition difficult.

· The fluctuations in drug levels may lead to precipitation of adverse effects especially of a drug with small Therapeutic Index (TI) whenever over medication occur.

Advantages of Extended Release Delivery System⁶:

· The extended release formulations reduce dosing frequency of drugs.

· The extended release formulations may maintain therapeutic concentrations.

· Reduce the toxicity by slowing drug absorption.

· The use of these formulations avoids the high blood concentration.

· Extended release formulations have the potential to improve the patient compliance and convenience.

· Minimize the local and systemic side effects.

· Increase the stability by protecting the drug from hydrolysis or other degradative changes in gastrointestinal tract.

· Improvement in treatment efficacy.

· Minimize drug accumulation with chronic dosing.

· Improve the bioavailability of some drugs.

· Usage of less total drug.

· Improve the ability to provide special effects. For example, Morning relief of arthritis through bed time dosing.

Disadvantages of Extended Release Delivery System⁶:

· Extended release formulation contains a higher drug load and thus any loss of integrity of the release characteristics of the dosage form.

· The larger size of extended release products may cause difficulties in ingestion or transit through gut.

· The release rates are affected by various factors such as food and the rate of transit through the gut.

· Some differences in the release rate from one dose to another dose but these have been minimized by modern formulations.

· High cost of preparation.

· Sometimes the target tissue will be exposed to constant amount of drug over extended period results in drug tolerance.

Rationale of Extended Drug Delivery⁷:

The main objective to formulate an API in an extended drug delivery system is related to its pharmacokinetics parameters. An appropriate formulation can make the absorption, distribution, metabolism and elimination (ADME) profile of a drug much more favourable. This change of the ADME can have a profound impact on many aspects of the clinical use of the drug from patient compliance and convenience to its very efficacy, tolerance and safety parameters.

AIM AND OBJECTIVE:

Aim of the work:

The aim of the study is to formulate and evaluate Cephalexin Extended release tablets using different polymers such as Xanthan gum, Karaya gum and Guar Gum.

Objective of the Study:

· Reduction in frequency of intakes.

· Reduce side effects.

· Uniform release of drug over time.

· Better patient compliance

The main objective of this study is to extend the drug release there by reducing the frequency of dosage.

Cephalexin is an antibiotic that can treat a number of bacterial infections. It kills gram-positive and some gram-negative bacteria by disrupting the growth of the bacterial cell wall.

Table1: Formulation composition for tablets

FORMULATION CODE	DRUG (MG)	POLYMRES (MG)			Magnesium stearate (MG)	Talc (MG)	MCC (MG)
FORMULATION CODE	DRUG (MG)	Xanthan gum	Karaya gum	Guar Gum	Magnesium stearate (MG)	Talc (MG)	MCC (MG)
C1	250	100	-	-	5	4	141
C2	250	150	-	-	5	4	91
C3	250	200	-	-	5	4	51
C4	250	-	100	-	5	4	141
C5	250	-	150	-	5	4	91
C6	250	-	200	-	5	4	51
C7	250	-	-	100	5	4	141
C8	250	-	-	150	5	4	91
C9	250	-	-	200	5	4	51

MATERIALS AND METHODS:

MATERIALS:

Cephalexin Procured from Aurobindo Pharma Ltd., India. Provided by SURA Labs, Dilsukhnagar, Hyderabad. Xanthan gum, Karaya gum, Guar Gum, Magnesium stearate, Talc and MCC purchased from Merck Specialities Pvt Ltd, Mumbai, India.

RESULTS AND DISCUSSION:

The present study was aimed to developing Extended release tablets of Cephalexin using various polymers. All the formulations were evaluated for physicochemical properties and in-vitro drug release studies.

Analytical Method:

Graphs of Cephalexin were taken in 0.1N HCl and in pH 6.8 phosphate buffer at 254nm and 257nm respectively.

Table2: Observations for graph of Cephalexin in 0.1N HCl (254nm)

Conc [µg/ml]	Absorbance
0	0
5	0.176
10	0.335
15	0.472
20	0.652
25	0.799

Table3: Observations for graph of Cephalexinin pH 6.8 phosphate buffer (257nm)

Concentration [µg/ml]	Absorbance
0	0
5	0.156
10	0.338
15	0.489
20	0.651
25	0.812

Figure1: Standard graph of Cephalexin in 0.1N HCl

Figure2: Standard graph of Cephalexin pH 6.8 phosphate buffer (257nm)

Table4: Pre-formulation parameters of Core blend

Formulation Code	Angle of Repose	Bulk density (gm/ml)	Tapped density (gm/ml)	Carr’s index (%)	Hausner’s Ratio
C1	26.0±0.02	0.55±0.01	0.73±0.03	17.6±0.01	1.24±0.01
C2	26.1±0.01	0.58±0.01	0.73±0.01	21.1±0.02	1.32±0.01
C3	27.5±0.04	0.57±0.03	0.67±0.01	21.6±0.02	1.30±0.02
C4	25.1±0.03	0.52±0.04	0.68±0.01	16.1±0.03	1.29±0.04
C5	27.5±0.02	0.57±0.02	0.67±0.02	20.8±0.03	1.26±0.04
C6	26.1±0.01	0.53±0.02	0.72±0.02	25.8±0.04	1.35±0.05
C7	25.1±0.03	0.56±0.03	0.71±0.02	21.1±0.04	1.27±0.04
C8	29.7±0.02	0.55±0.02	0.73±0.02	24.7±0.04	1.22±0.05
C9	28.0±0.01	0.57±0.01	0.69±0.01	17.6±0.05	1.24±0.04

Tablet powder blend was subjected to various pre-formulation parameters. The angle of repose values indicates that the powder blend has good flow properties. The bulk density of all the formulations was found to be in the range of 0.52±0.04 to 0.58±0.01 (gm/cm³) showing that the powder has good flow properties. The tapped density of all the formulations was found to be in the range of 0.67±0.01 to 0.73±0.03 showing the powder has good flow properties. The compressibility index of all the formulations was found to be below 25.8 which show that the powder has good flow properties. All the formulations has shown the Hausner’s ratio below 1.35 indicating the powder has good flow properties.

Quality Control Parameters For tablets:

Tablet quality control tests such as weight variation, hardness, and friability, thickness, and drug release studies in different media were performed on the compression coated tablet.

Table5: In-vitro quality control parameters for tablets

Formulation codes	Weight variation (mg)	Hardness(kg/cm²)	Friability (%loss)	Thickness (mm)	Drug content (%)
C1	498.35	5.3	0.62	3.85	98.35
C2	497.15	4.8	0.58	3.92	95.14
C3	500.04	5.0	0.76	4.72	99.68
C4	499.56	5.1	0.42	3.80	97.26
C5	495.28	5.5	0.39	4.15	99.18
C6	498.72	4.9	0.50	3.75	98.64
C7	496.65	4.8	0.67	4.21	97.42
C8	499.20	5.0	0.72	4.15	98.30
C9	497.51	5.4	0.83	4.10	99.15

All the parameters such as weight variation, friability, hardness, thickness and drug content were found to be within limits.

In-vitro drug release studies:

Table6: Dissolution data of Cephalexin tablets:

TIME (H)	Cumulative Percent Drug Dissolved
TIME (H)	C1	C2	C3	C4	C5	C6	C7	C8	C9
0	0	0	0	0	0	0	0	0	0
1	15.61	16.21	14.65	21.15	16.32	14.29	11.75	13.62	10.89
2	20.84	25.16	19.21	26.64	25.50	17.35	28.51	19.81	15.42
3	26.95	31.45	25.74	31.23	30.75	23.48	35.72	25.65	21.57
4	31.01	36.81	28.56	37.17	34.12	27.16	41.95	31.12	28.95
5	36.96	41.36	35.25	42.74	45.75	31.58	46.12	40.71	34.86
6	42.69	48.10	41.81	48.41	51.12	35.83	53.81	46.12	41.51
8	48.51	53.95	47.92	52.65	56.25	40.41	69.25	53.90	46.35
10	55.75	58.82	55.45	59.59	63.61	47.56	73.20	61.75	53.79
11	69.96	63.14	60.95	64.74	67.40	59.15	81.72	78.29	60.14
12	73.82	68.53	64.25	75.58	76.15	66.36	96.24	85.86	66.31
13	80.31	73.86	67.14	86.02	82.61	73.40		98.58	72.15
14	91.82	78.91	72.68	99.71	91.36	85.51			89.56

CONCLUSION:

Present work was directed towards the development and evaluation of extended release tablet dosage form of Cephalexin. Preformulation studies, identification of API and drug excipient compatibility study by using FTIR did not show any interaction between API and excipients. Extended release tablets of Cephalexin is to be prepared by direct compression method by using natural polymers like Xanthan gum, Karaya gum and Guar Gum. The evaluation studies pre and post compression parameters found to be within the acceptable limits. From the dissolution results among all the formulation C4 shows that 99.71% release at the end of 14 h. The cumulative percentage of drug release was increased by decrease in Karaya gum concentration. The kinetics studies formulation C4 was followed Zero order release kinetics.

АCKNOWLEDGEMENT:

The Authors arе thankful to Sura Labs, Dilshukhnagar, Hydеrabad for providing thе necessary facilities for the research work.

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Received on 17.02.2020 Modified on 11.03.2020

Res. J. Pharma. Dosage Forms and Tech.2020; 12(2): 53-57.

DOI: 10.5958/0975-4377.2020.00009.9