New Chandan PPT On Formulation and Evaluation of Sustain release matrix Tablet of Aceclofenac..pptx

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1. Rajasthan University of Health Sciences, Jaipur (Rajasthan) In partial fulfillment for the award of the degree of Master of Pharmacy in Pharmaceutics A thesis presentation submitted to the Under the guidance of Supervisor: Dr. VIJAY SHARMA, M.Pharm, Ph.D Professor, Department of Pharmaceutics Submitted by NAME: CHANDAN KUMAR Enrollment No: 2010/P-263 June 2025 GOENKA COLLEGE OF PHARMACY Formulation and Evaluation of Sustain release matrix Tablet of Aceclofenac

2. Dosage form The dosage form is described as the physical manifestation of a medicine, categorised as solid, liquid, or gas. Solid dosage forms are among the most prevalent pharmacological formulations utilised globally. They are multi-component systems that may exist in numerous forms, including powders, granules, compressed tablets, chewable tablets, and capsules. The pharmaceutical analysis of completed solid oral dosage forms demonstrates the essential factors for enhancing the uniqueness and efficacy of the delivery system, namely, the physical qualities and the condition of the drug component within the matrix.(1 ) Prior to considering other dosage forms for global regulation, the International Conference on Harmonisation (ICH) focused on solid oral dosage forms. The International Conference on Harmonisation (ICH) is a product of a cooperative effort by regulatory authorities and industry in Japan, the European Union, and the United States. It is utilised for the examination of pharmaceutical solid dosage forms, and there are a variety of approaches that are among those that are offered . 1. Introduction

3. Advantages of novel drug delivery system: Protection from physical and chemical degradation. Sustained delivery. Improved tissue macrophages distribution. Enhancement of stability. Enhancement of pharmacological activity. Protection from toxicity. Increased bioavailability. Enhancement of solubility.

4. Non steroidal anti-inflammatory drugs (NSAIDs): NSAIDs are being widely used all over the world for their anti-inflammatory, analgesic and anti-pyretic activities. Drug Class Example Salicylic acid derivates Aspirin Indole and indene acetic acids indomethacin, etodolac, sulindac Hetero-aryl acetic acids diclofenac, ketorolac, tolmetin Aryl- propionic acids ibuprofen, ketoprofen, flurbiprofen, naproxen, fenoprofen, oxaprozin, aceclofenac , fenclofenac Anthranilic acids mefenamic acid, meclofenanic acid Enolic acids piroxicam, tenoxicam, meloxicam Alkanones nabumetone Pyrazolidinediones pheynylbutazone, oxyphenylbutazone Diarylheterocycles lumiracoxib, rofecoxib, etoricoxib, valdecoxib, parecoxib, celecoxib Para-aminophenol derivates paracetamol (acetaminophen) Classification of NSAIDs : Aceclofenac is relatively a new NSAID. It is a potent COX-II blocker and inhibits the synthesis of prostaglandin E2. This review is significant in terms of information about the therapeutic application, adverse effects and the safety profile of aceclofenac .

5. 2. REVIEW OF LITERATURE Ali S.S et al., (2025) The innovative emulgel method combines emulsion and gel to provide controlled topical release of drugs. Adding an emulsion to a gel basis makes it more stable. The non-steroidal anti-inflammatory medicine aceclofenac has several applications in the treatment of osteoarthritis and rheumatoid arthritis. With the hope of improving skin penetration over current formulations, this study set out to create and evaluate an aceclofenac emulgel . We employed five different gelling agents: carbopol934, hydrophobic polymer complex, sodium alginate, and Na CMC. All of the formulations showed promising physical qualities when evaluated for drug release via dialysis membrane. The one with the best drug release efficiency was Carbopol 934. ( 10 Almurisi , S.H et al., (2024) The purpose of this research was to determine the impact of various polymer types on the buccal film characteristics of aceclofenac and to develop and characterise buccal film formulations using these materials. It is possible to create buccal films utilising several polymers, either alone or in combination, to provide the optimal drug release profile for a certain therapy objective. The buccal films' characteristics are also polymer-dependent, both in terms of kind and concentration. (13)

6. 3 . DRUG PROFILE Aceclofenac Aceclofenac is an oral non-steroidal anti-inflammatory drug (NSAID) with marked anti-inflammatory and analgesic properties used to treat osteoarthritis, rheumatoid arthritis and ankylosing spondylitis . It is reported to have a higher anti-inflammatory action or at least comparable effects than conventional NSAIDs. Aceclofenac potently inhibits the cyclo-oxygenase enzyme (COX) that is involved in the synthesis of prostaglandins, which are inflammatory mediators that cause pain, swelling, inflammation, and fever. Molecular Formula: C 16 H 13 CI 2 NO 4 IUPAC Name: 2-[(2, 6-Dichlorophenylamino) phenyl] acetoxy acetic acid. Molecular weight: 354.2 Category: Non-steroidal anti inflammatory drug. Solubility: It is practically insoluble in water; soluble in alcohol and methyl alcohol; It is freely soluble in acetone and dimethyl formamide . (38) Melting point: 149 - 150ºC

7. Mechanism of Action: Aceclofenac , by inhibiting COX-2, reduces the production of several inflammatory mediators such as prostaglandin E2 (PGE2), IL-1β, and TNF derived from the arachidonic acid (AA) pathway. The inhibition of IL-6 is believed to be facilitated by diclofenac , which is derived from aceclofenac . The inhibition of inflammatory cytokines leads to a reduction in the production of reactive oxygen species. Aceclofenac has been demonstrated to reduce the production of nitrous oxide in human articular chondrocytes. Volume of Distribution: The volume of distribution is approximately 25 L. Half-Life: The mean plasma elimination half-life is approximately 4 hours.

8. Drug -interaction: Aceclofenac has the potential to raise plasma concentrations of lithium, digoxin, and methotrexate ; it also has the ability to boost the action of anticoagulants ; it inhibits the activity of diuretics; it can increase the nephrotoxicity of cyclosporine; and it can cause convulsions when it is used in conjunction with quinolone antibiotics. Additionally , the concurrent use of Aceclofenac and antidiabetic medications may lead to hypo- or hyperglycemia, though such occurrences are infrequent. The co-administration of Aceclofenac with other NSAIDs leads to a higher incidence of adverse events. Dosage and administration: The usual dose of Aceclofenac is 100 mg given twice daily by mouth, one tablet in the morning and one in the evening . Storage: In an air tight container, protected from light. Uses: Aceclofenac is indicated for the management of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, dental pain, postoperative pain, dysmenorrhea, acute lumbago, musculoskeletal trauma, and gonalgia .

9. 4. AIM AND ODJECTIVES Aceclofenac is an analgesic, antipyretic, and non-steroidal anti-inflammatory drug. Its biological half-life is just four hours. The goal of the current research is to create an Aceclofenac sustained release matrix tablet that will increase patient compliance, enhance therapeutic effectiveness, minimise side effects, and need a lower dose with less toxicity. The current study's goal is to develop an Aceclofenac matrix tablet that will aid in the drug's long-term release to: Reduce dosing frequency. Prolong the pharmacological impact. Enhance patient compliance.

10. 5. PLAN OF WORK The goal of the current project is to create Aceclofenac -containing Sustain Release tablets and assess them according to a number of criteria. Literature Review Physicochemical Characterization of Drug: Physical appearance Melting point Preparation of Calibration curve of drug in distilled water and acid buffer using UV-Visible Spectroscopy Solubility determination Drug- excipient compatibility studies using FTIR Spectroscopy 3. Formulation of Sustain Release tablets containing Aceclofenac Using various combinations of Sustain Release forming polymers To optimize ratio of composition of drug & polymers used to prepare matrix tablets 4. Evaluation of the Sustain Release. A. Pre-compression evaluation parameters of Sustain . Angle of repose Bulk density Tapped density Carr’s Index Hausner’s Ratio B. Post- compression evaluation parameters of Sustain Release tablet Appearance, Shape and size Weight variation Hardness Friability Drug Content In-vitro Dissolution studies Accelerated Stability Studies

11. 6. METHODOLOGY MЕTHODOLOGY 6.1 Preformulation studies: 6.1.1 API characteristics: a. Organoleptic characteristics: The color, odor, and taste of Lornoxicam were evaluated and described using descriptive terminology b. Solubility Profile Conical flasks with fifty milliliters of Water, 0.1 N HCl , Acetate Buffer pH 4.5, Phosphate Buffer pH 6.8, Phosphate Buffer pH 7.8 each had the medication added in excess. Then, the conical flasks were manually shaken for a while. The conical flasks have been set on a rotary shaker and left there for a whole day. The mixtures had been passing through a 0.45-micron sieve after being shaken for 24 hours. Next, UV-Visible spectrophotometer readings were collected at each liquid's respective max to determine its absorbance( λmax ). The standard curve was used to determine drug concentrations, and the solubility of the drug in each solvent was used to determine the concentrations.

12. Analytісal mеthod dеvеlopmеnt : Dеtеrmіnatіon of absorptіon maxіma : 100 mg of pure Lornoxicam was dissolved in 100 ml of methanol to create a stock solution. Subsequently, 10 ml of this solution was diluted to 100 ml using 0.1 N HCl , resulting in a concentration of 100 μg /ml. From this, 10 ml was extracted and diluted to 100 ml with 0.1 N HCl (10 μg /ml). UV spectra of the phosphate buffer at pH 6.8 were obtained using a double beam UV/VIS spectrophotometer. The solution was analysed within the wavelength range of 200 to 400 nm. Preparation calibration curve: 100 milligrams of pure Lornoxicam was dissolved in 100 ml of methanol (stock solution). 10 ml of the aforementioned solution was taken and diluted to 100 ml using 0.1 N HCl (100 μg /ml). From this, 10 ml was extracted and diluted with 100 ml of 0.1 N HCl (10 μg /ml). The aforementioned solution was further diluted with 0.1N HCl to produce a series of dilutions containing 5, 10, 15, 20, and 25 μg /ml of Lornoxicam per ml of solution. The absorbance of the aforementioned dilutions was measured at 380 nm using a UV-spectrophotometer, with 0.1N HCl as the blank. A graph was constructed with Concentration on the X-axis and Absorbance on the Y-axis, resulting in a linear representation. The linearity of the standard curve was evaluated using the square of the correlation coefficient (R²), determined by least-squares linear regression analysis. The aforementioned procedure was repeated utilising pH 6.8 phosphate buffer solutions.

13. Drug – Еxсіpіеnt сompatіbіlіty studіеs Fourіеr Transform Infrared (FTІR) spесtrosсopy : The physical properties of the mixture were compared with those of the pure drug. Samples were completely mixed with 100 mg of potassium bromide IR powder and compacted under vacuum at a pressure of approximately 12 psi for 3 minutes.  The resultant disc was affixed in an appropriate holder within the Agilent spectrophotometer, and the IR spectrum was recorded from 3500 cm to 500 cm⁻¹. The resultant spectrum was analysed for any spectral alterations. 6.3. Preformulation parameters The quality of a tablet, once formulated by rule, is often determined by the quality of the physicochemical properties of blends. Numerous formulations and process variables are involved in mixing, and all of them can influence the characteristics of the resulting blends. The diverse characteristics of blends evaluated according to the Pharmacopoeia.

14. . 6.3.1 Anglе of rеposе : The frictional force in a loose powder may be quantified by the angle of repose. It is defined as the maximum angle possible between the surface of the pile of powder and the horizontal plane. If additional powder is introduced to the pile, it descends the sides of the pile until the mutual friction among the particles generates a surface angle that equilibrates with the gravitational force. The fixed funnel method was utilised to measure the angle of repose. A funnel was secured with its tip at a specified height (h) above a sheet of graph paper positioned on a level horizontal surface. The mixture was meticulously poured through the funnel until the apex of the conical pile just grazed the tip of the funnel. The radius (r) of the base of the conical pile was measured. The angle of repose was determined using the following formula: Tan θ = h / r Tan θ = Anglе of rеposе h = Hеіght of thесonе , r = Radіus of thе сonе basе Tablе 6.1: Anglе of Rеposе valuеs (as pеr USP) Anglе of Rеposе Naturе of Flow <25 Еxсеllеnt 25-30 Good 30-40 Passablе >40 Vеry poor

15. . Bulk dеnsіty : Density is defined as mass per unit volume. Bulk density is defined as the mass of the powder divided by the bulk volume and is expressed in gm /cm³. The bulk density of a powder mostly relies on particle size distribution, particle morphology, and the propensity of particles to agglomerate. Bulk density is crucial in determining the dimensions of containers required for the handling, shipping, and storage of raw materials and blends. It is also crucial in size blending equipment. Ten grammes of powder blend were sieved and introduced into a dry 20 ml cylinder without compaction. The powder was meticulously levelled without compaction, and the unsettled apparent volume, Vo, was recorded. The bulk density was computed with the formula: Bulk Dеnsіty = M / V o Whеrе , M = wеіght of samplе V o = apparеnt volumе of powdеr

16. . Bulk dеnsіty : Density is defined as mass per unit volume. Bulk density is defined as the mass of the powder divided by the bulk volume and is expressed in gm /cm³. The bulk density of a powder mostly relies on particle size distribution, particle morphology, and the propensity of particles to agglomerate. Bulk density is crucial in determining the dimensions of containers required for the handling, shipping, and storage of raw materials and blends. It is also crucial in size blending equipment. Ten grammes of powder blend were sieved and introduced into a dry 20 ml cylinder without compaction. The powder was meticulously levelled without compaction, and the unsettled apparent volume, Vo, was recorded. The bulk density was computed with the formula: Bulk Dеnsіty = M / V o Whеrе , M = wеіght of samplе V o = apparеnt volumе of powdеr

17. Drug – Еxсіpіеnt сompatіbіlіty studіеs Fourіеr Transform Infrared (FTІR) spесtrosсopy : The physical properties of the mixture were compared with those of the pure drug. Samples were completely mixed with 100 mg of potassium bromide IR powder and compacted under vacuum at a pressure of approximately 12 psi for 3 minutes.  The resultant disc was affixed in an appropriate holder within the Agilent spectrophotometer, and the IR spectrum was recorded from 3500 cm to 500 cm⁻¹. The resultant spectrum was analysed for any spectral alterations. 6.3. Preformulation parameters The quality of a tablet, once formulated by rule, is often determined by the quality of the physicochemical properties of blends. Numerous formulations and process variables are involved in mixing, and all of them can influence the characteristics of the resulting blends. The diverse characteristics of blends evaluated according to the Pharmacopoeia.

18. Mеasurеs of powdеr сomprеssіbіlіty : The Compressibility Index (Carr's Index) quantifies the porosity of a powder in relation to its compressibility. It is ascertained from the bulk and tapped densities. In theory, the less compressible a material, the more fluid it becomes. Consequently, it quantifies the relative significance of interparticulate interactions. In a free-flowing powder, such interactions are often less significant, resulting in bulk and tapped densities being closer in value. In less fluid materials, there are often heightened interparticle interactions, resulting in a more pronounced disparity between bulk and tapped densities. These distinctions are represented in the Compressibility Index, which is computed using the following formulas: Сarr’s Іndеx = [(tap - b) / tap] × 100 Whеrе , b = Bulk Dеnsіty Tap = Tappеd Dеnsіty Сarr’s іndеx Propеrtіеs 5 – 15 Еxсеllеnt 12 – 16 Good 18 – 21 Faіr to Passablе 2 – 35 Poor 33 – 38 Vеry Poor >40 Vеry Vеry Poor Tablе 6.2: Сarr’s іndеx valuе (as pеr USP)

19. Tappеd dеnsіty : Following the execution of the procedure outlined for the measurement of bulk density, the cylinder containing the sample was subjected to tapping using an appropriate mechanical tapped density tester, which delivers 100 drops per minute. This process was repeated until the difference between successive measurements was less than 2%, after which the tapped volume, V, was recorded to the nearest graduated unit. The tapped density was calculated in grammes per liters using the formula: Tap= M / V Whеrе , Tap= Tappеd Dеnsіty M = Wеіght of samplе V= Tappеd volumе of powdеr

20. Tappеd dеnsіty : Following the execution of the procedure outlined for the measurement of bulk density, the cylinder containing the sample was subjected to tapping using an appropriate mechanical tapped density tester, which delivers 100 drops per minute. This process was repeated until the difference between successive measurements was less than 2%, after which the tapped volume, V, was recorded to the nearest graduated unit. The tapped density was calculated in grammes per liters using the formula: Tap= M / V Whеrе , Tap= Tappеd Dеnsіty M = Wеіght of samplе V= Tappеd volumе of powdеr

21. 6.1.4 Solubility determination An excess of the drug was added to conical flasks, each containing 50 ml of distilled water, Acid buffer pH 1.2 and Phosphate buffer pH 6.8 respectively. Then conical flasks were shaken manually for some time. After that the conical flasks were kept on rotary shaker for 24 hours. After 24 hours of shaking, the solutions were filtered using a 0.45µ size filter. Then absorbances of the filtered liquids were taken by using a UV-Visible spectrophotometer at respective λmax . Concentrations of dissolved drug was calculated using the standard curve, which is equal to solubility of drug in respective solvent. Formulatіon No. Lornoxісam Xanthan gum Сhіtosan Guar gum Pvp k30 Mag.Stеaratе Talс MСС pH 102 F1 4 5 - - 12.5 2.5 2.5 QS F2 4 10 - - 12.5 2.5 2.5 QS F3 4 15 - - 12.5 2.5 2.5 QS F4 4 - 5 - 12.5 2.5 2.5 QS F5 4 - 10 - 12.5 2.5 2.5 QS F6 4 - 15 - 12.5 2.5 2.5 QS F7 4 - - 5 12.5 2.5 2.5 QS F8 4 - - 10 12.5 2.5 2.5 QS F9 4 - - 15 12.5 2.5 2.5 QS

22. 6.5. Еvaluatіon of post compression paramеtеrs for prеparеd Tablets The formulated tablets were examined for their physicochemical properties, including weight variation, hardness, thickness, friability, and drug content. 6.5.1 Wеіght varіatіon tеst : To examine weight variation, twenty tablets were individually and collectively weighed on a digital weighing balance. The average weight of a tablet was calculated from the total weight. The weight variation test would be an adequate method for determining the uniformity of medication content. No more than two individual weights may deviate from the average weight by the percentage shown in the following table, and none may deviate by more than twice that percentage. The mean and deviation were calculated. The percentage deviation was calculated using the following formula. % Dеvіatіon = ( Іndіvіdual wеіght – Avеragе wеіght / Avеragе wеіght ) × 100

23. 6.5. Еvaluatіon of post compression paramеtеrs for prеparеd Tablets The formulated tablets were examined for their physicochemical properties, including weight variation, hardness, thickness, friability, and drug content. 6.5.1 Wеіght varіatіon tеst : To examine weight variation, twenty tablets were individually and collectively weighed on a digital weighing balance. The average weight of a tablet was calculated from the total weight. The weight variation test would be an adequate method for determining the uniformity of medication content. No more than two individual weights may deviate from the average weight by the percentage shown in the following table, and none may deviate by more than twice that percentage. The mean and deviation were calculated. The percentage deviation was calculated using the following formula. % Dеvіatіon = ( Іndіvіdual wеіght – Avеragе wеіght / Avеragе wеіght ) × 100 Avеragе wеіght of tablеt (mg) (І.P) Avеragе wеіght of tablеt (mg) (U.S.P) Maxіmum pеrсеntagе dіffеrеnсе allowеd Lеss than 80 Lеss than 130 10 80-250 130-324 7.5 Morе than Morе than 324 5

24. 6.5.3 Thісknеss : Tablet thickness is a significant characteristic in reproducing appearance. Tablet thickness is a significant characteristic in reproducing appearance. The average thickness of core and coated tablets is calculated and presented with deviation. 6.5.4 Frіabіlіty : The mechanical strength of tablets is measured. The Roche friabilator was utilised to ascertain the friability by adhering to the specified procedure. Preweighed tablets were positioned in the friabilator . The tablets were rotated at 25 revolutions per minute for 4 minutes, totalling 100 rotations. Upon completion of the test, the tablets were reweighed; the weight loss of the tablets serves as the measure of friability and is expressed as a percentage. % Frіabіlіty = [ ( W1-W2) / W] × 100 Whеrе , W1 = Іnіtіal wеіght of thrее tablеts W2 = Wеіght of thе thrее tablеts aftеr tеstіng

25. Dеtеrmіnatіon of drug сontеnt : Tablets were analysed for their pharmaceutical composition. Ten tablets were finely powdered, and quantities of the powder equivalent to the weight of one tablet were accurately weighed and transferred to a 100 ml volumetric flask containing 50 ml of water, where they were allowed to stand to ensure complete solubility of the medicine. The mixture was adjusted to volume using media. The solution was appropriately diluted, and the absorption was measured using a UV-Visible spectrophotometer. The drug concentration was determined using the calibration curve. 6.5.6 Іn vіtro drug rеlеasе studіеs Dіssolutіon paramеtеrs : Apparatus -- USP-ІІ, Paddlе Mеthod Dіssolutіon Mеdіum -- 0.1 N HСl , pH 6.8 Phophatе buffеr RPM -- 50 Samplіng іntеrvals ( hrs ) -- 0.5,1,2,3,4,5,6,7,8,10,11,12 Tеmpеraturе -- 37°с + 0.5°с

26. Proсеdurе : 900 ml of 0.1 HCl was placed in a vessel, and the USP apparatus II (Paddle Method) was assembled. The medium was let to equilibrate to a temperature of 37°C ± 0.5°C. The tablet was positioned in the vessel, and the system was operated for two hours. Subsequently, the 0.1 N HCl media was removed, and a pH 6.8 phosphate buffer was introduced. The process was continued for up to 12 hours at 50 RPM. At certain time intervals, 5 ml of the sample was withdrawn, filtered, and subsequently replaced with 5 ml of media. Appropriate dilutions were prepared using media and analysed spectrophotometrically at 277 nm using a UV-spectrophotometer.   Applanations of Rеlеasе Rate Kіnеtісs to Dissolution Data: Diverse models were evaluated to elucidate the kinetics of drug release. To analyse the mechanism of the drug release rate kinetics of the dosage form, the acquired data were fitted into zero-order, first-order, Higuchi, and Korsmeyer-Peppas release models.

27. Zеro ordеr rеlеasе ratе kіnеtісs : To study thе zеro – ordеr rеlеasе kіnеtісs thе rеlеasе ratе data ar е fіttеd to thе followіng еquatіon . F = K o t Whеrе , ‘F’ іs thе drug rеlеasе at tіmе‘t ’, and ‘ K o ’ іs thе zеro ordеr rеlеasе ratесonstant . Thе plot of % drug rеlеasе vеrsus tіmеіs lіnеar . Fіrst ordеr rеlеasе ratе kіnеtісs : Thе rеlеasе ratе data arе fіttеd to thе followіng еquatіon Log (100-F) = kt A plot of log сumulatіvе pеrсеnt of drug rеmaіnіng to bе rеlеasеd vs. Tіmе іs plottеd thеn іt gіvеs fіrst ordеr rеlеasе .

28. Hіguсhі rеlеasе modеl : To study thе Hіguсhі rеlеasе kіnеtісs , thе rеlеasе ratе data wеrе fіttеd to thе followіngеquatіon . F = k t1/2 Whеrе , ‘k’ іs thе Hіguсhісonstant . Іn hіguсhі modеl , a plot of % drug rеlеasе vеrsus squarе root of tіmе іs lіnеar . Korsmеyеr and Pеppas rеlеasе modеl : The mechanism of drug release was assessed by plotting the logarithm of the percentage of drug released against the logarithm of time, in accordance with the Korsmeyer-Peppas equation. The exponent 'n' signifies the drug release mechanism, determined by the slope of the straight line. M t / M ∞ = K t n Where, Mt/M∞ denotes the fraction of drug released at time 't', k signifies a constant, and 'n' represents the diffusional exponent, which characterises the kind of release mechanism during the dissolution process. In non- Fickian release, the value of n ranges from 0.5 to 1.0; in the case of Fickian diffusion, n equals 0.5; for zero-order release (case II transport), n equals 1; and for super case II transport, n exceeds 1. In this model, a graph of log (Mt/M∞) vs log (time) is linear.

29. Hіxson-Сrowеll rеlеasе modеl : (100-Q t ) 1/3 = 100 1/3 – K HС .t Whеrе , k іs thе Hіxson-Сrowеll ratе сonstant . The Hixson-Crowell model delineates the release of medicines from an insoluble matrix mostly by erosion. Where there is a variation in surface area and diameter of particles or tablets.

30. 6.4 Formulatіon dеvеlopmеnt of Tablеts : All the formulations were prepared using direct compression. The compositions of various formulations are presented in Table 6.3. The tablets were formulated according to the procedure outlined below, with the objective of extending the release of Lornoxicam . The whole weight of the tablet was regarded as 100 mg. Proсеdurе : Lornoxісam and all other іngrеdіеnts wеrе іndіvіdually passеd through sіеvе no  60. All thе іngrеdіеnts wеrе mіxеd thoroughly by trіturatіng up to 15 mіn . The powder mixture was lubrісatеd wіth talс . The tablets were prepared by using dіrесt compression method.

31. 6.4 Formulatіon dеvеlopmеnt of Tablеts : All the formulations were prepared using direct compression. The compositions of various formulations are presented in Table 6.3. The tablets were formulated according to the procedure outlined below, with the objective of extending the release of Lornoxicam . The whole weight of the tablet was regarded as 100 mg. Proсеdurе : Lornoxісam and all other іngrеdіеnts wеrе іndіvіdually passеd through sіеvе no  60. All thе іngrеdіеnts wеrе mіxеd thoroughly by trіturatіng up to 15 mіn . The powder mixture was lubrісatеd wіth talс . The tablets were prepared by using dіrесt compression method.

32. 6.4 Formulatіon dеvеlopmеnt of Tablеts : All the formulations were prepared using direct compression. The compositions of various formulations are presented in Table 6.3. The tablets were formulated according to the procedure outlined below, with the objective of extending the release of Lornoxicam . The whole weight of the tablet was regarded as 100 mg. Proсеdurе : Lornoxісam and all other іngrеdіеnts wеrе іndіvіdually passеd through sіеvе no  60. All thе іngrеdіеnts wеrе mіxеd thoroughly by trіturatіng up to 15 mіn . The powder mixture was lubrісatеd wіth talс . The tablets were prepared by using dіrесt compression method.

33. S. No. Ingredients Source   Aceclofenac Mepro Pharmaceuticals Pvt. Ltd. Surendranagar, Gujarat   Indion 244 Ind Swift   Carbopol 934P Ind Swift   Magnesium Stearate Central Drug House   Talc Central Drug House Materials and Methods List of Chemicals Table 6.1: List of chemicals

34. Evaluation of Pre-compression parameters Powder mixture formulated was evaluated for different pre-compression parameters using standard procedures. The evaluation were done in triplicate (n=3) and mean was calculated. 6.3.1 Angle of repose Angle of repose is used to determine flow property of the powder. It is defined as the maximum angle possible between the surface of a pile of the powder and horizontal plane. It can be measured by the funnel method. In this method, the funnel is placed above graph paper at distance of 6 cm. The powder is kept in the funnel and allowed to flow. The powder forms a pile. The height and diameter of powder pile is measured. The angle of repose is calculated using following formula: θ= 〖tan〗^(-1) (h/r) Where, “θ” is angle of repose, “h” is height of pile and “r” is radius of the base of pile.

35. Bulk density The bulk density and tapped density are evaluated to determine filling of powder in the die. To determine bulk density, weighed amount of powder mixtures is filled in a measuring cylinder, and the bulk volume of powder is noted. The following formula is used to determine the bulk density: 6.3.3 Tapped density To determine tapped density, weighed amount of powder mixtures is filled in a measuring cylinder, tapped for 50 times and the tapped volume of powder is noted. The following formula is used to determine the tapped density:  

36. Carr’s Index It represents the powder flow properties. It can be computed by the formula: Where D t : tapped density of the powder D b : bulk density of the powder 6.3.5 Hausner’s ratio Hausner’s ratio is also used to represent flow properties of powder. It is calculated by using following formula and it is expressed in percentage:  

37. In-vitro Dissolution Studies Dissolution studies of sustain release tablets are performed to ensure sustained release of the drug ( Aceclofenac ) for longer duration. Dissolution studies of prepared sustain release tablets was performed in two steps. Initially, Acid buffer pH 1.2 (corresponding to gastric environment) was used as dissolution media for initial two hours. Then, the dissolution media was replaced with Phosphate buffer pH 6.8 (corresponding to intestinal environment) as dissolution media for next ten hours. Paddle apparatus was used for dissolution studies at 50 RPM and 37 ±0.5 C . Accelerated Stability Studies Short term accelerated stability studies of the selected formulation were carried out at 40 C/75%RH over a period of 3 months. The matrix tablets were wrapped with aluminium foil, and stored in humidity controlled oven for 3 months. Samples were analysed for residual drug contents at time interval of 15 days .  

38. S. No. Equipment Manufacturer/ Make   Melting Point Apparatus Electronics India   UV-Visible Spectrophotometer Shimadzu (UV-1800)   Electronic balance Shimadzu (BL-220H)   FT-IR Bruker (Alpha II)   pH meter Systronics   Vernier Caliper Aerospace   Tablet punching machine Cadmach   Tablet Hardness Tester Instrument India   Friability Test Apparatus Instrument India   Dissolution Test Apparatus Electrolab , TDT-08 L   Bulk Density Apparatus Instrument India   Humidity controlled oven Rolex India Lis of Equipments : List of Equipments

39. 7. RESULTS AND DISCUSSION 7.1 Physicochemical Characterization of Drug ( Preformulation Studies): Preformulation studies were performed for following parameters. 7.1.1 Physical Appearance The physical form and color of the drug ( Aceclofenac ) was observed visually. Physical form: Solid powder Color: White Odor: Odorless 7.1.2. Melting Point The melting point determination of the drug was done by using the melting point apparatus. A small amount of pure drug of Aceclofenac was taken in a capillary tube and it was kept in the melting point apparatus. The reading of melting point was taken in triplicate and noted. The melting point of Aceclofenac was found to be 148°C - 150 °C , which is same as documented (149 °C ).

40. 7. RESULTS AND DISCUSSION R Е SULTS AND D І S С USS І ON The current study aimed to develop sustained release tablets of Lornoxicam utilising various polymers. All formulations were assessed for physicochemical properties and in vitro drug release studies. 7.1 Preformulation studies: 7.1.1 API characteristics: i . Organoleptic characteristics: Table 7.1 Organoleptic property of Drug Properties Result Taste and odour bitter taste and a lack of a distinct odor Color Yellow solid powder ii. Flow Properties: Table 7.2: Pre- formulation studies of API S. No. Tests Results 1 Bulk Density 0.2413gm/ml 2 Tapped Density 0.3953gm/ml 3 Compressibility index 37.55% 4 Hausner’s ratio 1.26

41. 7. RESULTS AND DISCUSSION Sr. No. Buffers Solubility (mg/ml) 1 Water 0.92 2 0.1 N HCl 653 3 Acetate Buffer pH 4.5 165 4 Phosphate Buffer pH 6.8 1.6 5 Phosphate Buffer pH 7.8 0.7 Discussion: based on the above pre-formulation results it was observed that the flow was poor and wet granulation method was suitable. iii. Solubility Profile: Table 7.3: Solubility data of API

42. Сonсеntratіon [µg/ml] Absorbanсе 5 0.217 10 0.438 15 0.688 20 0.876 25 1.1 ornoxicam exhibited maximum absorbance at 380 nm in simulated gastric fluid (pH 1.2) and at 385 nm in phosphate buffer (pH 6.8), respectively. b. Preparation of Calibration Curve Graphs of Lornoxicam were obtained in Simulated Gastric fluid (pH 1.2) and in pH 6.8 phosphate buffer at 380 nm and 385 nm, respectively. Tabl е 7.4: Obs е rvat і ons for graph of Lornox іс am і n 0.1N H С l (380 nm) С on се ntrat і on [µg/ml] Absorban се 0 0 5 0.217 10 0.438 15 0.688 20 0.876 25 1.1 The estimation of Lornoxicam using UV spectrophotometric method at λ max 380 nm in 0.1N hydrochloric acid shown high reproducibility, and this method was employed in the study. The correlation coefficient for the standard curve was determined to be about 1 within the concentration range of 5-25 μ g/ml. The generated regression equation is y = 0.044x + 0.001.

43. 8. REFERENCES Yesuneh TM. 2020. Pharmaceutical solid oral dosage form analysis: Literature Review. Op Acc J Bio Sci & Res. 4(1), 1-7. Khan MG. 2017. The Novel Drug Delivery System. WorldJournal of Pharmacy andPharmaceuticalSciences . 6(7), 477-487. Patil S, Mhaiskar A, Mundhada D. 2016. A Review on Novel Drug Delivery System: A RecentTrend . International Journal of Current Pharmaceutical & Clinical Research. 6(2), 89-93. Swaleh MM, Nisa Z, Ali SA, Khan MA, Shehnaz S. 2020. A Detailed Review on Oral Controlled Release Matrix Tablets. Int. J. Pharm. Sci. Rev. Res. 64(2), 27-38. Mondal N. 2018. The Role of Matrix Tablet in Drug DeliverySystem.International Journal of Applied Pharmaceutics. 10, 1-6. Tripathi KD, Controlled Drug Delivery System, 1-36. DeRuiter J. Principles of Drug Action 2, Fall 2002. Non- SteroidalAntiinflammatoryDrugs (NSAIDS), 1-26. Welch E. 2017. Non-steroidal anti-inflammatory drugs (NSAIDs) Part I Anaesthesia Refresher Course – 2017, University of Cape Town, 09, 01-06. Bushra R, Shoaib MH, Naeem MI, Aslam N. 2013. Acelofenac : A New Effective and SafeNSAID , IJDDT, 4(1), 34-42.

44. Almurisi , S.H., Mohammed, A., Qassem , F., Jehad , H., Jassim , A., AL- Japairai , K. and Sammour , R.M., 2024. Development and In Vitro Evaluation of Aceclofenac Buccal Film. Current Drug Discovery Technologies, 21(3), pp.46-55. Jaiswal , H., Ansari , M.T., Mahmood , T., Ahsan , F., Ansari , V.A. and Ahmad, U., 2024. Aceclofenac loaded microspheres: Formulation and evaluation of novel preprogrammed drug delivery for the treatment of arthritis. Intelligent Pharmacy, 2(1), pp.69-82. Ravi Sharma, Mayank Bansal , Alok Garg , Vikas Agarwal , & Deeksha Sharma. (2023). Formulation and Evaluation of Sustain Release Matrix Tablet of Aceclofenac . International Journal of Health Advancement and Clinical Research ( tz ), 1(1), 6-11. Ashwani Singh, Mayank Bansal , Vikas , Rakesh Kumar Gupta, & Deeksha Sharma. (2023). Formulation and Evaluation of Enteric Coated Tablet of Aceclofenac . International Journal of Health Advancement and Clinical Research ( tz ), 1(1).01-05. Bitay , E., Gergely , A.L. and Szabó , Z.I., 2023. Optimization and Production of Aceclofenac -Loaded Microfiber Solid Dispersion by Centrifugal Spinning. Pharmaceutics, 15(9), p.2256.