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Table 29: Kinetic Model Fitting For Optimised Formulation (F9)

Table 29 Kinetic Model Fitting For Optimised Formulation (F9)

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Figure 1: Classification of Modified Release Drug Delivery System"!
Figure 1: Classification of Modified Release Drug Delivery System"!
Controlled Release This term on the other hand, has a meaning that goes beyond the scope of sustained drug action. It also implies a predictability & reproducibility in the drug release kinetics, which means that the release of drug ingredient from a controlled delivery system proceeds at a rate profile that is not only predictable kinetically, but also reproducible from one unit to another. The term sustained release has been constantly used to describe a pharmaceutical dosage form formulated to retard the release of a therapeutic agent such that its appearance in the systemic circulation is delayed &/or prolonged & its plasma profile is sustained in duration.
Controlled Release This term on the other hand, has a meaning that goes beyond the scope of sustained drug action. It also implies a predictability & reproducibility in the drug release kinetics, which means that the release of drug ingredient from a controlled delivery system proceeds at a rate profile that is not only predictable kinetically, but also reproducible from one unit to another. The term sustained release has been constantly used to describe a pharmaceutical dosage form formulated to retard the release of a therapeutic agent such that its appearance in the systemic circulation is delayed &/or prolonged & its plasma profile is sustained in duration.
Figure 3: Kinetic scheme of conventional dosage form.
Figure 3: Kinetic scheme of conventional dosage form.
Figure 4: Kinetic scheme of non-conventional dosage form. Alternatively speaking the absorption of drug across a biological membrane is the rate limiting step. For non- immediate release dosage forms, Kr<<<Ka i.e. the
Figure 4: Kinetic scheme of non-conventional dosage form. Alternatively speaking the absorption of drug across a biological membrane is the rate limiting step. For non- immediate release dosage forms, Kr<<<Ka i.e. the
Figure 6: Schematic Representation of Diffusion Type Matrix System.
Figure 6: Schematic Representation of Diffusion Type Matrix System.
Figure5: Schematic Representation of Diffusion Type Reservoir System.
Figure5: Schematic Representation of Diffusion Type Reservoir System.
Figure 7: Structure of Lornoxicam. Proprietary names Lornoxi, Lorna, Lornex, Lornox Losnasafe, Lorsid, LRN, Nyox, Telos, Xefo, Xefocam Zeficam.
Figure 7: Structure of Lornoxicam. Proprietary names Lornoxi, Lorna, Lornex, Lornox Losnasafe, Lorsid, LRN, Nyox, Telos, Xefo, Xefocam Zeficam.
Aloe verais well known for its marvelous medicinal properties. These plants are one of the richest sources of health for human beings coming from nature. It has been grown as an ornamental plant widely. The natural range of A.vera is unclear, as the species has been widely cultivated throughout the world. | Products of the plant
Aloe verais well known for its marvelous medicinal properties. These plants are one of the richest sources of health for human beings coming from nature. It has been grown as an ornamental plant widely. The natural range of A.vera is unclear, as the species has been widely cultivated throughout the world. | Products of the plant
Figure 13: Aloe barbadensis leaves. Like other NSAIDs, it appears to interact with warfarin, sulphonyl ureas, digoxin and furosemide. It is not affected by the co-administration of ranitidine, aluminium, magnesium and calcium containing antacids. Cimetidinen co-administration inhibits elimination of Lornoxicam resulting in significant increase in steady state Cmax and AUC (area under curve) values and a reduction in apparent plasma clearance. Lornoxicam displaces glibenclamide from its protein binding site leading to enhanced glibenclamide effect.
Figure 13: Aloe barbadensis leaves. Like other NSAIDs, it appears to interact with warfarin, sulphonyl ureas, digoxin and furosemide. It is not affected by the co-administration of ranitidine, aluminium, magnesium and calcium containing antacids. Cimetidinen co-administration inhibits elimination of Lornoxicam resulting in significant increase in steady state Cmax and AUC (area under curve) values and a reduction in apparent plasma clearance. Lornoxicam displaces glibenclamide from its protein binding site leading to enhanced glibenclamide effect.
Figure 14: Different chemical constituents of aloe vera. Anthraquinones: Aloin (barbaloin), — Isobarloin, Anthranol, Aloetic acid, Anthracene, ester of Cinnamic acid, Aloe-emodin, Emodin, Chrysophanoic acid, Ethereal oil as well as Resistannol.
Figure 14: Different chemical constituents of aloe vera. Anthraquinones: Aloin (barbaloin), — Isobarloin, Anthranol, Aloetic acid, Anthracene, ester of Cinnamic acid, Aloe-emodin, Emodin, Chrysophanoic acid, Ethereal oil as well as Resistannol.
Figure 17: Isabgol Seeds. Pharmaceutical use: Aloe barbadensis miller leaves mucilage suitable for use as a release retardant in the manufacture of sustained release matrix tablets & tablet binder, suspending agent it is having good swelling, good flow and suitability for matrix formulations.
Figure 17: Isabgol Seeds. Pharmaceutical use: Aloe barbadensis miller leaves mucilage suitable for use as a release retardant in the manufacture of sustained release matrix tablets & tablet binder, suspending agent it is having good swelling, good flow and suitability for matrix formulations.
Mechanism™”! Substance which absorbs water and due to its enhanced swelling properties, forms an emollient gel that facilitates the passage of intestinal contents and stimulates bowel movement. Because isabgol forms a bulk on swelling, it is classified as a bulk-laxative. It is usually effective within 8-12 hrs. Since isabgol is unaffected by the digestive enzymes and not absorbed into the system, it does not affect the absorption of other nutrients. It passes unchanged through the intestines. Therefore the action of isabgol is purely mechanical, as it relives constipation by mechanically stimulating bowel movement. This process closely approximates the body’s own mechanism. The Jelly-like substance has, in addition, the triple-refined isabgol in nature care contains large quantities of a gelatinous remarkable capacity to absorb bacterial and other toxins in the intestines. In short, isabgol works partly by lubrication and partly by increasing the bulk of the intestinal contents, which stimulates bowel movement.
Mechanism™”! Substance which absorbs water and due to its enhanced swelling properties, forms an emollient gel that facilitates the passage of intestinal contents and stimulates bowel movement. Because isabgol forms a bulk on swelling, it is classified as a bulk-laxative. It is usually effective within 8-12 hrs. Since isabgol is unaffected by the digestive enzymes and not absorbed into the system, it does not affect the absorption of other nutrients. It passes unchanged through the intestines. Therefore the action of isabgol is purely mechanical, as it relives constipation by mechanically stimulating bowel movement. This process closely approximates the body’s own mechanism. The Jelly-like substance has, in addition, the triple-refined isabgol in nature care contains large quantities of a gelatinous remarkable capacity to absorb bacterial and other toxins in the intestines. In short, isabgol works partly by lubrication and partly by increasing the bulk of the intestinal contents, which stimulates bowel movement.
Figure 19: Structure of Ethyl Cellulose. Isabgol husk and seeds contain pentosan and aldobionic acid. Mucilage is also present in the epidermis seed. Some other important constituents are Fixed oil and proteins. Hydrolytic products are rhamnose, arabinose and galacturonic acid. Plantago seeds contain, Iridoids. The mucilage contains weakly acidic Arabinoxylans composed of a xylan backbone linked with Arabinose, Rhamnose, and Galacturonic acid units. Also 17.4% protein, 6.7% fat, 24.6% total dietary fibre, 19.6%
Figure 19: Structure of Ethyl Cellulose. Isabgol husk and seeds contain pentosan and aldobionic acid. Mucilage is also present in the epidermis seed. Some other important constituents are Fixed oil and proteins. Hydrolytic products are rhamnose, arabinose and galacturonic acid. Plantago seeds contain, Iridoids. The mucilage contains weakly acidic Arabinoxylans composed of a xylan backbone linked with Arabinose, Rhamnose, and Galacturonic acid units. Also 17.4% protein, 6.7% fat, 24.6% total dietary fibre, 19.6%
insoluble fibre, 5.0% soluble fibre, and a combustion heat of 4.75 kcal/g. Osborne fractionation (based on solubility) yielded albumin 35.8%, globulin 23.9%, and Prolamin 11.7%. The oil from plantago seeds had a high percentage of Linoleic acid (40.6%) and oleic acid (39.1%) and a minor proportion of Linolenic acid (6.9%). In vitro protein digestibility of the plantago seed was 77.5%, suggesting a highly digestible protein. Lysine content was 6.82 2/100 g of protein.
insoluble fibre, 5.0% soluble fibre, and a combustion heat of 4.75 kcal/g. Osborne fractionation (based on solubility) yielded albumin 35.8%, globulin 23.9%, and Prolamin 11.7%. The oil from plantago seeds had a high percentage of Linoleic acid (40.6%) and oleic acid (39.1%) and a minor proportion of Linolenic acid (6.9%). In vitro protein digestibility of the plantago seed was 77.5%, suggesting a highly digestible protein. Lysine content was 6.82 2/100 g of protein.
7. Description: Hypromellose is an odourless and tasteless, white or creamy-white fibrous or granular powder. Ethyl cellulose is widely used in oral and topica pharmaceutical formulations. It is also used in food products. It is not metabolized following ora consumption and is therefore a non-caloric substance. It is generally regarded as a nontoxic, non-allergenic, and non irritating material. It is not metabolized and therefore is not recommended for parenteral products; parentera use may be harmful to the kidneys. Ethyl cellulose is widely used in oral and _ topical pharmaceutical formulations; the main use of ethyl cellulose in oral formulations is as a hydrophobic coating
7. Description: Hypromellose is an odourless and tasteless, white or creamy-white fibrous or granular powder. Ethyl cellulose is widely used in oral and topica pharmaceutical formulations. It is also used in food products. It is not metabolized following ora consumption and is therefore a non-caloric substance. It is generally regarded as a nontoxic, non-allergenic, and non irritating material. It is not metabolized and therefore is not recommended for parenteral products; parentera use may be harmful to the kidneys. Ethyl cellulose is widely used in oral and _ topical pharmaceutical formulations; the main use of ethyl cellulose in oral formulations is as a hydrophobic coating
A high compactability is required to obtain sufficient strength of the final tablets. The ability of a powder to compact into tablets dependents on a balance between the plastic deformation and the powder particles. Brittle brittle fracture properties of fracture is required to reduce sensitivity towards lubricants, and plasticity is necessary to reduce the distance between the particles. The various pharmaceutical lactose deformation properties. different alpha products have Below 45-micron, monohydrate lactose crystals behave ductile and above 45-micron, the crystals behave brittle.
A high compactability is required to obtain sufficient strength of the final tablets. The ability of a powder to compact into tablets dependents on a balance between the plastic deformation and the powder particles. Brittle brittle fracture properties of fracture is required to reduce sensitivity towards lubricants, and plasticity is necessary to reduce the distance between the particles. The various pharmaceutical lactose deformation properties. different alpha products have Below 45-micron, monohydrate lactose crystals behave ductile and above 45-micron, the crystals behave brittle.
PREPARATION OF MATRIX TABLETS OF LORNOXICAM: Granules were prepared as follows.
PREPARATION OF MATRIX TABLETS OF LORNOXICAM: Granules were prepared as follows.
Table 5: Protocol for drug-excipients compatibility. At the time of physical observation after the completior of study, there were no colour changes, lump formation or any significant visual changes observed as against the control or initial results.
Table 5: Protocol for drug-excipients compatibility. At the time of physical observation after the completior of study, there were no colour changes, lump formation or any significant visual changes observed as against the control or initial results.
Table 12: In Vitro Release Study Parameters.
Table 12: In Vitro Release Study Parameters.
5. Swelling Index Where, PD = Percentage deviation, W avg = Average weight of tablet, W initial = individual weight of tablet. Swelling index of the dosage form is conducted by using USP dissolution apparatus- in 900 ml of pH 6.8 phosphate buffer which is maintained at 37+40.5°C, rotated at 50 rpm. At selected regular intervals, the tablet is withdrawn the excess water was blotted with tissue paper. This procedure was repeated until the tablet reaches constant weight. The swelling index was calculated by using following formula.
5. Swelling Index Where, PD = Percentage deviation, W avg = Average weight of tablet, W initial = individual weight of tablet. Swelling index of the dosage form is conducted by using USP dissolution apparatus- in 900 ml of pH 6.8 phosphate buffer which is maintained at 37+40.5°C, rotated at 50 rpm. At selected regular intervals, the tablet is withdrawn the excess water was blotted with tissue paper. This procedure was repeated until the tablet reaches constant weight. The swelling index was calculated by using following formula.
Table 13: Mechanism of Drug Release as per Korsmeyer Equation / Peppa’s Model. For Fickian release ‘n’ = 0.5 while for anomalous (non — Fickian) transport ‘n’ ranges between 0.5 and 1.0. The result of in vitro drug release study of all the formulation as shown below.
Table 13: Mechanism of Drug Release as per Korsmeyer Equation / Peppa’s Model. For Fickian release ‘n’ = 0.5 while for anomalous (non — Fickian) transport ‘n’ ranges between 0.5 and 1.0. The result of in vitro drug release study of all the formulation as shown below.
FTIR study of Lornoxicam: FTIR spectra of the selected (Optimized) formulations were taken and Selected formulations were stored at different storage conditions at elevated temperatures such as 25°C+ 2°C / 60% + 5% RH, 30°C + 2°C / 65% +5% RH and 40°C + 2°C / 75% + 5% RH for 90 days. The samples were withdrawn at intervals of fifteen days and checked for physical changes. COMPATABILITY STUDIES OF DRUG WITH EXCIPIENTS: - SEM has been used to determine the surface topography, texture and to examine the morphology of fractured or sectioned surface. The examination of the surface of polymeric drug delivery system can provide important information about the porosity and micro structure of device. The optimized formulation was selected for scanning electron microscopy (SEM) by using JEOL- JSM-840A, Japan. The tablet surface morphology was studied at 2™, 6" and 12™ hours. Method
FTIR study of Lornoxicam: FTIR spectra of the selected (Optimized) formulations were taken and Selected formulations were stored at different storage conditions at elevated temperatures such as 25°C+ 2°C / 60% + 5% RH, 30°C + 2°C / 65% +5% RH and 40°C + 2°C / 75% + 5% RH for 90 days. The samples were withdrawn at intervals of fifteen days and checked for physical changes. COMPATABILITY STUDIES OF DRUG WITH EXCIPIENTS: - SEM has been used to determine the surface topography, texture and to examine the morphology of fractured or sectioned surface. The examination of the surface of polymeric drug delivery system can provide important information about the porosity and micro structure of device. The optimized formulation was selected for scanning electron microscopy (SEM) by using JEOL- JSM-840A, Japan. The tablet surface morphology was studied at 2™, 6" and 12™ hours. Method
Figure 27: FT-IR of Lornoxicam+ Lactose.
Figure 27: FT-IR of Lornoxicam+ Lactose.
Figure 31: FT-IR of Lornoxicam + Mg. Stearate. igure29: FT-IR of Lornoxicam+ PVP K30.
Figure 31: FT-IR of Lornoxicam + Mg. Stearate. igure29: FT-IR of Lornoxicam+ PVP K30.
Figure 30: FT-IR of Mg. Stearate.
Figure 30: FT-IR of Mg. Stearate.
Figure 33: FT-IR of Lornoxicam + Talc.
Figure 33: FT-IR of Lornoxicam + Talc.
Overly IR spectrum of Lornoxicam(RS) matches and optimised formulation F-9 was found to be similar. Importantly, finger print region of both tested compounds was found to be matching. Indicates no signs of drug-excipients in incompatility. SEM was operated at 15 KV. The condenser lens position was maintained at a constant level. SEM study further confirmed both diffusion and __ erosion mechanisms to be operative during drug release from the optimized batch of matrix tablet(F-9). SEM photomicrograph of the matrix tablet taken at different time intervals after the dissolution experiment showed that matrix was intact and pores had formed throughout the matrix. SEM photomicrographs with graphs of tablet surface at different time intervals also showed that erosion of matrix increased respect to time indicated by the photomicrographs at 2™, 6", and 12™hrs revealing pores with increasing diameter.
Overly IR spectrum of Lornoxicam(RS) matches and optimised formulation F-9 was found to be similar. Importantly, finger print region of both tested compounds was found to be matching. Indicates no signs of drug-excipients in incompatility. SEM was operated at 15 KV. The condenser lens position was maintained at a constant level. SEM study further confirmed both diffusion and __ erosion mechanisms to be operative during drug release from the optimized batch of matrix tablet(F-9). SEM photomicrograph of the matrix tablet taken at different time intervals after the dissolution experiment showed that matrix was intact and pores had formed throughout the matrix. SEM photomicrographs with graphs of tablet surface at different time intervals also showed that erosion of matrix increased respect to time indicated by the photomicrographs at 2™, 6", and 12™hrs revealing pores with increasing diameter.
As with SEM high vacuum is required for image formation and samples must be thoroughly desiccated before entering the vacuum chamber, therefore samples were thoroughly dried after swelling for analysis. The dried samples were mounted on sample holder using double sided adhesive carbon tape. The
As with SEM high vacuum is required for image formation and samples must be thoroughly desiccated before entering the vacuum chamber, therefore samples were thoroughly dried after swelling for analysis. The dried samples were mounted on sample holder using double sided adhesive carbon tape. The
Figure 35 (a, b, c): SEM studies of optimised formulation Preliminary confirmatory tests for dried gums and mucilage Carbohydrate, Mucilage, Polysaccharides, Alkaloids and Tanninsin table below. Preliminary phytochemical tests of the four below mentioned extracts carried out shows the presence of
Figure 35 (a, b, c): SEM studies of optimised formulation Preliminary confirmatory tests for dried gums and mucilage Carbohydrate, Mucilage, Polysaccharides, Alkaloids and Tanninsin table below. Preliminary phytochemical tests of the four below mentioned extracts carried out shows the presence of
Figure 36: UV —Spectrum of Lornoxicamin 0.1 N HCL.
Figure 36: UV —Spectrum of Lornoxicamin 0.1 N HCL.
Figure 37: UV —Spectrum of Lornoxicamin pH 6.8 phosphate buffer. UV —Spectrum of Lornoxicamin pH 6.8 phosphate buffer UV -Spectrum of Lornoxicam in pH 6.8 phosphate buffer(Figure 37) shows that the drug had A max of 376nm.
Figure 37: UV —Spectrum of Lornoxicamin pH 6.8 phosphate buffer. UV —Spectrum of Lornoxicamin pH 6.8 phosphate buffer UV -Spectrum of Lornoxicam in pH 6.8 phosphate buffer(Figure 37) shows that the drug had A max of 376nm.
Figure 39: Standard plot of Lornoxicamin pH 6.8 Phosphate buffer. The standard plot of Lornoxicam is as shown in (Figure 39). The data of absorbance is shown in table 18. The correlation coefficient obtained was0.9991 and equation of regression line was y =0.0296x. Standard plot of Lornoxicamin ph 6.8 Phosphate buffer Figure 38: Standard plot of Lornoxicamin 0.1 N HCL.
Figure 39: Standard plot of Lornoxicamin pH 6.8 Phosphate buffer. The standard plot of Lornoxicam is as shown in (Figure 39). The data of absorbance is shown in table 18. The correlation coefficient obtained was0.9991 and equation of regression line was y =0.0296x. Standard plot of Lornoxicamin ph 6.8 Phosphate buffer Figure 38: Standard plot of Lornoxicamin 0.1 N HCL.
Table 18: Standard plot of Lornoxicam in ph 6.8 Phosphate buffer.
Table 18: Standard plot of Lornoxicam in ph 6.8 Phosphate buffer.
Evaluation of Lornoxicam Tablets Pre Compression Parameters Table 19: Data for blend evaluation of formulation (F-1 to F-6 Table 20: Data for blend evaluation of formulation (F-7 to F-12)
Evaluation of Lornoxicam Tablets Pre Compression Parameters Table 19: Data for blend evaluation of formulation (F-1 to F-6 Table 20: Data for blend evaluation of formulation (F-7 to F-12)
‘able 21: Physical properties of tablet formulation (F-1 to F- 6) of Lornoxicam sustained release matrix tablets.
‘able 21: Physical properties of tablet formulation (F-1 to F- 6) of Lornoxicam sustained release matrix tablets.
Table 22: Physical properties of tablet formulation (F-7 toF- 12) of Lornoxicam sustained release matrix tablets.
Table 22: Physical properties of tablet formulation (F-7 toF- 12) of Lornoxicam sustained release matrix tablets.
Table 23: Weight variation of formulations F1 to F6 of Lornoxicam sustained release tablets.
Table 23: Weight variation of formulations F1 to F6 of Lornoxicam sustained release tablets.
Table 24: Weight variation of formulations F7 to F12 of Lornoxicam sustained release tablets. the same volume of fresh medium was replaced every time. Sample were filtered through 0.45 um filter pape: and the content of Lornoxicam was _ determinec spectrophotometrically at a wavelength of 376nm fo: first 2 hr and then after take in 376nm. The release studies were conducted and results were noted ir respective tables.
Table 24: Weight variation of formulations F7 to F12 of Lornoxicam sustained release tablets. the same volume of fresh medium was replaced every time. Sample were filtered through 0.45 um filter pape: and the content of Lornoxicam was _ determinec spectrophotometrically at a wavelength of 376nm fo: first 2 hr and then after take in 376nm. The release studies were conducted and results were noted ir respective tables.
Table 26: Percentage drug release of formulationsF-7to F-12.
Table 26: Percentage drug release of formulationsF-7to F-12.
Figure 40: In Vitro Dissolution Profile of F-1 to F-6 Formulations.
Figure 40: In Vitro Dissolution Profile of F-1 to F-6 Formulations.
Figure 41:Jn Vitro Dissolution Profile of F-7 to F-12 Formulations.
Figure 41:Jn Vitro Dissolution Profile of F-7 to F-12 Formulations.
Figure 42: Kinetic Model Fitting For Optimised Formulation F-9. Table 28: Correlation coefficients of different mathematical models for formulations F-7 to F-12.
Figure 42: Kinetic Model Fitting For Optimised Formulation F-9. Table 28: Correlation coefficients of different mathematical models for formulations F-7 to F-12.
Table 31: Friability and Hardness of optimized formulation after stability studies.
Table 31: Friability and Hardness of optimized formulation after stability studies.
Table 32: % Drug release and Drug content of optimized formulation after stability studies
Table 32: % Drug release and Drug content of optimized formulation after stability studies
the inhibition of cyclooxygenase, which suppresses the production of prostaglandins and thromboxanes thereby reducing pain and inflammation. The analgesic activity is related to balanced inhibition of COX-1 and COX-2. unlike some NSAIDs, the inhibition of cyclooxygenase by lornoxicam does not result in an increase in leukotriene formation, and the shunting of arachidonic acid to the 5-lipoxygenase cascade is therefore not expected, which minimizes the risk of some adverse events, for example, allergic reactions. The half-life of Lornoxicam is 3-4 hours. The absolute bioavailability (calculated as AUC) of XEFO film-coated tablets is 90— 100%. Lornoxicam is metabolized completely, and approximately 2/3 is eliminated via the liver and 1/3 via the kidney as inactive substance. All these criteria responsible for selection of drug.
the inhibition of cyclooxygenase, which suppresses the production of prostaglandins and thromboxanes thereby reducing pain and inflammation. The analgesic activity is related to balanced inhibition of COX-1 and COX-2. unlike some NSAIDs, the inhibition of cyclooxygenase by lornoxicam does not result in an increase in leukotriene formation, and the shunting of arachidonic acid to the 5-lipoxygenase cascade is therefore not expected, which minimizes the risk of some adverse events, for example, allergic reactions. The half-life of Lornoxicam is 3-4 hours. The absolute bioavailability (calculated as AUC) of XEFO film-coated tablets is 90— 100%. Lornoxicam is metabolized completely, and approximately 2/3 is eliminated via the liver and 1/3 via the kidney as inactive substance. All these criteria responsible for selection of drug.
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