Design expert supported mathematical optimization of repaglinide gastroretentive floating tablets: In vitro and in vivo evaluation

Naveen, N. Raghavendra; Gopinath, Chakka; Rao, D. Subba

doi:10.1016/j.fjps.2017.05.003

Cited by 37 publications

(26 citation statements)

References 22 publications

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“…OG was extracted as reported formerly by our research group [21]. TOG was synthesized by the esterification of OG with Thioglycolic acid (TGA) in presence of HCl.…”

Section: Synthesis Of Thiolated Okra Gum [Tog]mentioning

confidence: 99%

“…This will make us think about the modified dissolution method for preciseness in IVIVC. The in vitro drug release data were evaluated kinetically using various mathematical models such as zero order, first order, Higuchi and Korsmeyer-Peppas models [21]. The 'n' value (release exponent from Peppas model) and r 2 (regression values) for all the formulations (both paddle and modified basket method) were shown in Table 4.…”

Section: In Vitro Drug Release Studiesmentioning

confidence: 99%

“…Repaglinidepossesses a unique non-specific anti-diabetic action. Repaglinideacts by stimulating the insulin release by binding to the specific sites on β islet cells of the pancreas and blocks ATP (Adenosine triphosphate) dependent K+ channel, however, its use is limited due to short t 1/2 (1 h) and a bioavailability of 50% [21]. In addition to this, Repaglinide produces hypoglycemic conditions on oral administration and imposes side effects such as skeletal muscle pain, headache and some GIT effects [22,23].…”

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confidence: 99%

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Okra-Thioglycolic Acid Conjugate—Synthesis, Characterization, and Evaluation as a Mucoadhesive Polymer

Naveen¹,

Gopinath

Kurakula

2020

Processes

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The success of mucoadhesive drug delivery systems relies on the type of polymer used, which becomes adhesive naturally upon hydration. Intended polymers should be able to maintain prolonged contact with biological membranes, and to protect or cater the drug to a prolonged period. Most of the hydro polymers form weak non-covalent bonds, that hinder localization of dosage forms at specific sites resulting in therapeutic inefficiency. This can be overcome by the thiol functionalization of natural polymers. In the present study, natural okra gum (OG) was extracted, followed by thiolation (TOG) and evaluated for mucoadhesion property and its role in enhancing the efficacy of repaglinide as a model drug (short-acting Type II antidiabetic drug). The thiol functionalization of OG (TOG) was confirmed by a Fourier-transform infrared spectroscopy (FTIR) study that showed a polyhedral to a spherical shape that had a rougher surface. Differential scanning calorimetry (DSC) and X-Ray Diffraction (XRD) studies of TOG indicated a decline in endothermic transition temperature and high crystallinity, respectively, in comparison to OG. CSFR (Crushing Strength: Friability Ratio), weight and thickness variations of repaglinidetablets formulated using TOG were >80% and <2.5% respectively. The highest swelling index (107.89 ± 1.99%) and strong mucoadhesion due to high disulfide bonds were observed for repaglinide TOG tablets in comparison to RG OG tablets. In-vitro release studies indicated a controlled drug release from thiolated formulations proportional to the concentration of thiomers that have a good correlation with in-vivo studies. Pharmacokinetic studies indicated higher AUC (area under the curve), longer t 1/2 with thiomers. and Level A IVIV (in vitro in vivo) correlation was established from the bioavailability and dissolution data. Consequently, all the obtained results suggest that thiomers based formulations can be promising drug delivery systems, even in targeting onerous mucosal surfaces like nasal, ocular or vaginal.by suitable approaches such as thiolation, to employ in mucoadhesion drug delivery systems [9]. Nevertheless, to date, there has been no research reported in demonstrating the synthesis of thiolated okra gum (TOG) and evaluating its use in designing mucoadhesive drug delivery systems.The term bio adhesion depicts the adhesion of the polymer to the biological membrane. Specifically, when the adhesion is limited to the mucosal surface it is named mucoadhesion [10]. The conception of mucoadhesion, as well as mucoadhesion polymers, was developed in the mid 1980s as an intriguing methodology especially for targeting the delivery of drugs at a site or at the absorption window. Mucoadhesive polymers become adhesive on hydration and characterized to have prolonged contact and residence time with the mucous membrane. [11]. Despite a few notable exceptions, gastric mucoadhesive systems do not reach their full potential. The success of the majority of the first generation mucoadhesion polymers was limited owing to thei...

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“…OG was extracted as reported formerly by our research group [21]. TOG was synthesized by the esterification of OG with Thioglycolic acid (TGA) in presence of HCl.…”

Section: Synthesis Of Thiolated Okra Gum [Tog]mentioning

confidence: 99%

Section: In Vitro Drug Release Studiesmentioning

confidence: 99%

mentioning

confidence: 99%

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Okra-Thioglycolic Acid Conjugate—Synthesis, Characterization, and Evaluation as a Mucoadhesive Polymer

Naveen¹,

Gopinath

Kurakula

2020

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“…Each response was set for the goals, and the desirability plot for both responses showed a maximum D value of 0.852, which was obtained at optimum concentrations of the independent variables [40,41]. Accordingly, the use of such conditions would achieve the required viscosity before and after gelation with less gelation temperature.…”

Section: Preparation Of Ro-nts Loaded In Situ Gelmentioning

confidence: 99%

Preparation and Optimization of In Situ Gel Loaded with Rosuvastatin-Ellagic Acid Nanotransfersomes to Enhance the Anti-Proliferative Activity

2020

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The objective of this study was to develop an optimized sustained-release nanotransfersomes (NTS) based in situ gel formulation of rosuvastatin (RO) combined with ellagic acid (EA) antioxidant, to enhance cytotoxic and anti-proliferative activity against tongue carcinoma. The concentrations of lecithin, Tween 80, and d-tocopherol polyethylene glycol succinate (TPGS) were considered as independent variables. Particle size, entrapment, and stability were selected as dependent variables. The obtained formulation containing 25% lecithin, 20% Tween 80, and TPGS 15% fulfilled the prerequisites of the optimum formulation. RO-NTS loaded in situ gel was prepared and optimized for concentrations of Poloxamer 407, and Carbopol, using statistical design. Drug release from in situ gel showed a sustained release profile. The RO IC50 was decreased by half for the in situ gel in comparison to plain RO and RO-EA-NTS. A significant amount of caspase-3 was detected in all the formulation treatments. The studies indicated that EA's synergistic anti-oxidant effect owing to a high affinity to the PGP efflux transporter and higher penetration in the RO-NTS formulation led to a higher inhibition against human chondrosarcome-3 cancer cell lines. RO-EA NTS-loaded in situ gel had a sustained release that could be significant in localized therapy as an alternative to surgery in the treatment of aggressive tongue carcinoma. sensitivity of lung cancer and human leukemia cell lines to anthracyclines [6,7]. Administration of statins combined with antioxidant compounds of natural origin can yield better results as shown in the combination of simvastatin and alpha-lipoic acid that improved toxicity against breast carcinoma cell lines [8].Transferosomes, defined as vesicular colloidal dispersions composed mainly of phospholipids and nonionic surfactants acting as edge activators (EA), have attracted a great deal of attention in the field of drug delivery [9]. The presence of such EA weakens the bonds between phospholipids molecules and imparts the property of elasticity onto transferases making them ultra deformable vesicles. Transferosomes have several advantages that make them successful vesicular drug delivery systems, including (a) being biodegradable and biocompatible with human body, and (b) the ability of EA to solubilize and stabilize poorly soluble drugs owing to their surface activity, low toxicity, enhanced tissue targeting capacity, and ability to obtain prolonged drug release [10][11][12]. RO, also known as "superstatin," is the most effective antihyperlipidemic agent in the statins family. It is more efficient and attains fewer side effects compared to other statins although it exhibits poor solubility and poor bioavailability [13]. Several studies have proven the anticancer activity of RO. It showed cytotoxic effects against thyroid cancer cells in vitro as it increased the caspase-3 activity and apoptosis confirmed by DNA fragmentation analysis [14], and reduced viability in cervical, hepatic, and breast cancer cell lines [15]. Mor...

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“…These values were used to measure the significance of the coefficients of the model. The effect of independent variables on responses was further elucidated and analyzed by response surface methodology (RSM) [27]. In RSM, the main effects and interaction effects can be understood by utilizing three-dimensional response surface graphs (RSG).…”

Section: Preparation Of Chitosan-coated Sim-qrc Npsmentioning

confidence: 99%

In Situ Gel Loaded with Chitosan-Coated Simvastatin Nanoparticles: Promising Delivery for Effective Anti-Proliferative Activity against Tongue Carcinoma

Kurakula

Naveen²

2020

Marine Drugs

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The goal of this study is to develop optimized chitosan-coated Simvastatin (SIM) nanoparticles (NPs) loaded in an in situ gel (ISG) formulation via a face-centered central composite design (FCCCD). Coated SIM-NPs were doped with Quercetin (QRC) using a modified nanoprecipitation method. The concentrations of poloxamer 188 (A) and chitosan (B) at five different levels, plus/minus alpha (+1.414 and −1.414: axial points), plus/minus 1 (factorial points) and the center point were optimized for particle size (PS-Y1), entrapment efficacy (EE-Y2) and stability index (SI-Y3). Based on the desirability approach, a formulation containing poloxamer 188 0.24% and chitosan 0.43% renders the prerequisites of optimum formulation for preparing SIM-QRC NP-loaded ISG. Scanning microscopy showed spherical SIM-NPs, indicating monodispersity in the range of 0.50 ± 0.04 nm with a charge of +32.42 mV. The optimized formulation indicated the highest EE 79.67% and better stability at 4 • C. Drug release from SIM-QRC NP-loaded ISG was slower to plateau by up to 96 h and, at the end of 168 h, only 65.12% of SIM was released in a more controlled manner in comparison to SIM-QRC NPs and plain SIM. ISG formulation showed a considerable increase in apoptosis occurrence through caspase-3 mediation and it also enhanced the tumor suppressor protein levels. Enhanced biological activity of SIM was observed due to QRC enabling promising drug and polymer synergistic interaction. The proposed formulation can provide a breakthrough in localized therapy, overcoming the potential drawbacks of systemic chemotherapy for tongue carcinoma.

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Design expert supported mathematical optimization of repaglinide gastroretentive floating tablets: In vitro and in vivo evaluation

Cited by 37 publications

References 22 publications

Okra-Thioglycolic Acid Conjugate—Synthesis, Characterization, and Evaluation as a Mucoadhesive Polymer

Okra-Thioglycolic Acid Conjugate—Synthesis, Characterization, and Evaluation as a Mucoadhesive Polymer

Preparation and Optimization of In Situ Gel Loaded with Rosuvastatin-Ellagic Acid Nanotransfersomes to Enhance the Anti-Proliferative Activity

In Situ Gel Loaded with Chitosan-Coated Simvastatin Nanoparticles: Promising Delivery for Effective Anti-Proliferative Activity against Tongue Carcinoma

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