Sathyaseelan, V (2017) Formulation Development and Invitro Evaluation of Sustained Release Matrix Tablets of Nateglinide by Using Natural Polymers. Masters thesis, J.K.K. Nattraja College of Pharmacy, Kumarapalayam.
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Abstract
AIM : Recently, sustained release drug delivery system has become the standards in the modern pharmaceutical design and intensive search has been undertaken in achieving much better drug product effectiveness, reliability and safety. Oral sustain release medication will continue to account for the largest share of drug delivery systems, due to ease of its formulation as compared to other systems. The biggest ascent of these type of systems is the ease with which they can be prepared on the large scale, and hence, easy commercialization. For treating diabetes, it has been considered important that both a post prandial blood glucose level and a fasting blood glucose level are decreased to make them to normal levels. Other antidiabetics are primarily used for decreasing either a post prandial blood glucose level or a fasting blood glucose level to make it close to a normal level, but nateglinide has been used to control both post prandial blood glucose level as well as a fasting blood glucose level. Nateglinide is a BCS class II (Insoluble, highly permeable) drug. The plasma half life of nateglinide is 1.5h. The usual oral dosage regimen is 60— 180mg taken 3 times a day for nateglinide immediate release tablets. The nateglinide controlled or sustained release formulation would be more useful than the nateglinide immediate release tablets from the view point of avoidance of side effect, or of easy control of both PBG and FBG to enable control of both PBG and FBG for moderate and severe diabetes patients. Thus, there is a need to formulate oral sustained drug delivery system of nateglinide. The oral sustained release drug delivery system of nateglinide can be formulated using various synthetic as well as natural hydrophilic polymers. The biodegradable nature and easy availability of the natural polymers makes them suitable for using as a sustained release polymer. The natural polymers also exhibit a rheological synergism between them when two polymers are mixed together. By using this property of the natural polymers can be used to reduce the total polymer concentration from the sustained release matrix tablet and once a day formulation of the nateglinide can be formulated containing least amount of polymer. Nateglinide [N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine] is a novel mealtime glucose regulator approved for the treatment of type II diabetes mellitus. Nateglinide has a rapid onset and short duration of insulinotropic action that results in reduction of mealtime glucose rise and lowers the postabsorptive potential for hypoglycemia in humans and experimental animals.OBJECTIVE: To prepare and evaluate once a day sustained release matrix tablet of Nateglinide. To reduce the total polymer concentration using rheological synergism between two natural gums. To study the invitro performance of matrix tablet.SUMMARY:Nateglinide [N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine] is a novel, highly physiologic, mealtime glucose regulator approved for the treatment of type II diabetes mellitus. Nateglinide is a BCS class II (Insoluble, highly permeable) drug. The plasma half life of nateglinide is 1.5h and bioavailability of 73%. The usual oral dosage regimen is 60— 180mg taken 3 times a day for nateglinide immediate release tablets. The controlled or sustained release formulation of nateglinide would be more useful than the nateglinide immediate release tablets from the view point of avoidance of side effect, improvement of compliance to patients and to enable control of both post prandial blood glucose level and fasting blood glucose level for moderate and severe diabetes patients. Hence, an attempt was made to develop a sustained-release (SR) oral dosage form of nateglinide instead of IR tablet. The present work studied the natural polymer based once a day matrix tablet of nateglinide. From the wide range of hydrophilic polymers, k – carrageenan, λ – carrageenan and locust bean gum. Combinations of the two different gums kcarrageenan and locust bean gum and λ-carrageenan and locust bean gum were formulated in different ratios 20:80, 40:60, 50:50, 60:40 and 80:20 to exploit rheological synergism between two gums. Further the formulations were prepared dorm the formulation which exhibited maximum retardation such that each contains 10% less polymer concentration than the previous formulation in order to achieve the once a day matrix tablet of nateglinide containing least amount of polymer. The blends were prepared by non-aqueous wet granulation techniques with lactose as a diluent in formulations. The dried blends were compressed with other necessary excipients. The tablets were evaluated for hardness, thickness, drug content uniformity, in-vitro drug release studies for 24 hours (USP dissolution apparatus II, phosphate buffer-pH 6.8, 50 rpm, 37±0.5ºC), water uptake studies, swelling studies and in of the matrix tablet. The amount of Nateglinide released from the tablet formulations was estimated at 210nm using a UV spectrophotometer. The kinetic analysis of selected formulations were performed and found to follow Korsmeyer-Peppas model through non-fickian transport mechanism. The following conclusions can be drawn from the above study.Nateglinide [N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine] is a novel, highly physiologic, mealtime glucose regulator approved for the treatment of type II diabetes mellitus. Nateglinide is a BCS class II (Insoluble, highly permeable) drug. The plasma half life of nateglinide is 1.5h and bioavailability of 73%. The usual oral dosage regimen is 60— 180mg taken 3 times a day for nateglinide immediate release tablets. The controlled or sustained release formulation of nateglinide would be more useful than the nateglinide immediate release tablets from the view point of avoidance of side effect, improvement of compliance to patients and to enable control of both post prandial blood glucose level and fasting blood glucose level for moderate and severe diabetes patients. Hence, an attempt was made to develop a sustained-release (SR) oral dosage form of nateglinide instead of IR tablet. The present work studied the natural polymer based once a day matrix tablet of nateglinide. From the wide range of hydrophilic polymers, k – carrageenan, λ – carrageenan and locust bean gum. Combinations of the two different gums kcarrageenan and locust bean gum and λ-carrageenan and locust bean gum were formulated in different ratios 20:80, 40:60, 50:50, 60:40 and 80:20 to exploit rheological synergism between two gums. Further the formulations were prepared dorm the formulation which exhibited maximum retardation such that each contains 10% less polymer concentration than the previous formulation in order to achieve the once a day matrix tablet of nateglinide containing least amount of polymer. The blends were prepared by non-aqueous wet granulation techniques with lactose as a diluent in formulations. The dried blends were compressed with other necessary excipients. The tablets were evaluated for hardness, thickness, drug content uniformity, in-vitro drug release studies for 24 hours (USP dissolution apparatus II, phosphate buffer-pH 6.8, 50 rpm, 37±0.5ºC), water uptake studies, swelling studies and in of the matrix tablet. The amount of Nateglinide released from the tablet formulations was estimated at 210nm using a UV spectrophotometer. The kinetic analysis of selected formulations were performed and found to follow Korsmeyer-Peppas model through non-fickian transport mechanism. The following conclusions can be drawn from the above study.Nateglinide [N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine] is a novel, highly physiologic, mealtime glucose regulator approved for the treatment of type II diabetes mellitus. Nateglinide is a BCS class II (Insoluble, highly permeable) drug. The plasma half life of nateglinide is 1.5h and bioavailability of 73%. The usual oral dosage regimen is 60— 180mg taken 3 times a day for nateglinide immediate release tablets. The controlled or sustained release formulation of nateglinide would be more useful than the nateglinide immediate release tablets from the view point of avoidance of side effect, improvement of compliance to patients and to enable control of both post prandial blood glucose level and fasting blood glucose level for moderate and severe diabetes patients. Hence, an attempt was made to develop a sustained-release (SR) oral dosage form of nateglinide instead of IR tablet. The present work studied the natural polymer based once a day matrix tablet of nateglinide. From the wide range of hydrophilic polymers, k – carrageenan, λ – carrageenan and locust bean gum. Combinations of the two different gums kcarrageenan and locust bean gum and λ-carrageenan and locust bean gum were formulated in different ratios 20:80, 40:60, 50:50, 60:40 and 80:20 to exploit rheological synergism between two gums. Further the formulations were prepared dorm the formulation which exhibited maximum retardation such that each contains 10% less polymer concentration than the previous formulation in order to achieve the once a day matrix tablet of nateglinide containing least amount of polymer. The blends were prepared by non-aqueous wet granulation techniques with lactose as a diluent in formulations. The dried blends were compressed with other necessary excipients. The tablets were evaluated for hardness, thickness, drug content uniformity, in-vitro drug release studies for 24 hours (USP dissolution apparatus II, phosphate buffer-pH 6.8, 50 rpm, 37±0.5ºC), water uptake studies, swelling studies and in of the matrix tablet. The amount of Nateglinide released from the tablet formulations was estimated at 210nm using a UV spectrophotometer. The kinetic analysis of selected formulations were performed and found to follow Korsmeyer-Peppas model through non-fickian transport mechanism. The following conclusions can be drawn from the above study.From the results obtained we can conclude that the polymers selected for the study, can be used individually for the sustained drug delivery of nateglinide locust bean gum was used in combination with k-carrageenan and λ-carrageenan in 60:40 and 20:80 ratios respectively with least in vitro drug release and can be used to reduce the concentration of polymer from the tablet.30% polymer reduction in case of k-carrageenan and locust bean gum and 20% with λ-carrageenan and locust bean gum combination was achieved.CONCLUSION:Once a day sustained release matrix tablets of nateglinide was prepared by using natural polymers k-carrageenan,lambda carrageenan and locust bean gum. Natural polymers were selected due to their easy availability and cheaper in coast and we can get standard uniformity and combinations of two different gums carrageenan and locust been gum were formulated in different ratios to exploit the rheological synergism between two gums in order to achive once a day matrix tablets of nateglinide further formulations were prepared from the formulations exhibited maximum retardation the controlled or sustained release formulations of nateglinide would be more useful than the nateglinide immediate release tablets from the new point of side effects improvement of compliance to patients and to enable to control of both post prandial blood glucose level and fasting blood glucose level for moderate and sever diabates patients. Hence an attempt was made to develop a sustained release oral dosage form of nateglinide instead of immediate release tablet.
| Item Type: | Thesis (Masters) |
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| Uncontrolled Keywords: | Invitro Evaluation ; Sustained Release Matrix Tablets ; Nateglinide ; Using Natural Polymers |
| Subjects: | PHARMACY > Pharmaceutics |
| Depositing User: | Ravindran C |
| Date Deposited: | 20 Dec 2017 07:57 |
| Last Modified: | 20 Dec 2017 07:57 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/4555 |
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