Natural gum as mucoadhesive controlled release carriers: evaluation of Cefpodoxime Proxetil by D-Optimal design technique

Abstract

The present study deals with the development of mucoadhesive controlled release tablets of Cefpodoxime Proxetil to increase the gastric residence time and thus prolong drug release, reduce dosing frequency and improve oral bioavailability. Tablets were prepared using sodium alginate and karaya gum, a natural polymer, with a synthetic polymer hydroxypropylmethylcellulose (K100LV) and Karaya gum with HPMC K100LV in various ratios to optimize the drug release profile using D-Optimal technique. Pre- and post-compression parameters of tablets prepared with various formulations (S1–S9, C1–C9) were evaluated. The FTIR and DSC studies revealed that no physiochemical interaction between excipients and drug. The formulation S7 showed prolonged drug release, and the mechanism of drug release from the optimized formulation was confirmed using the Korsmeyer–Peppas model to be non-Fickian release transport and n value was found 0.605 indicating both diffusion and erosion mechanism from these natural gums. The optimized formulation showed mucoadhesive strength >35?g. An in vivo study was performed on rabbits using an X-ray imaging technique. The radiological evidence suggests that the tablets adheres (more than 10 hours) to a rabbit’s stomach. No significant changes were found in the physical appearance, drug content, mucoadhesive study and in vitro dissolution pattern after storage at 40?°C/75% relative humidity for 3 months.     

Mucoadhesive bilayer buccal tablet of carvedilol-loaded chitosan microspheres: in vitro,pharmacokinetic and pharmacodynamic investigations

A multiple-unit system comprising mucoadhesive bilayer buccal tablets of carvedilol-loaded chitosan microspheres (CMs) was developed to improve bioavailability and therapeutic efficacy of carvedilol. Drug-loaded CMs were prepared by spray drying, evaluated for powder and particle characteristics, and optimized batch of CMs was compressed into bilayer buccal tablets using Carbopol. Tablets were evaluated for physicochemical parameters, in vitro drug release, in vivo pharmacokinetic and pharmacodynamic studies. Optimized formulation, CMT1 (CMT, chitosan microsphere tablet) showed maximum mucoadhesive force (50?±?1.84?dyne/cm²), exhibited 73.08?±?3.05% drug release and demonstrated zero-order kinetics with non-Fickian release mechanism. Pharmacokinetic studies in rabbits showed significantly higher C_max (71.26?±?6.45?ng/mL), AUC_0–10 (AUC, area under the curve 390.75?±?5.23?ng/mL/h) and AUC_0–∞ (664.72?ng/mL/h) than carvedilol oral tablet. Pharmacodynamic studies confirmed reduction in mean arterial pressure, heart rate, body weight and triglyceride on administration of bilayer buccal tablet compared to oral carvedilol tablet. Multiple-unit system exhibited enhanced bioavailability and sustained release of carvedilol, indicating its improved therapeutic potential for the treatment of hypertension.     

Iron oxide induced enhancement of mucoadhesive potential of Eudragit RLPO: formulation,evaluation and optimization of mucoadhesive drug delivery system

Objectives: The objective of the study was to investigate the effect of iron oxide in the development of mucoadhesive tablets of cinnarizine using Eudragit RLPO polymer. A simplex lattice design was employed for optimizing the drug delivery system.

Methods: Different concentrations of Eudragit RLPO (X₁), iron oxide (X₂) and PVP K 30 (X₃) were taken as independent variables and mucoadhesive strength, t_50%, t_90%, MDT and tablet tensile strength were the selected response variables. Contour and 3D plots were drawn to portray the relationship between independent and response variables. Ex vivo studies were performed for the determination of mucoadhesive strength of formulated tablets employing texture analyzer. ATR-FTR, DSC and zeta potential determination were conducted for drug-excipient and ionic interaction studies.

Results: Friability, hardness and tensile strength of mucoadhesive tablet formulation were found to be 0.42 ± 0.21%, 3.93 ± 1.57 kg/cm² and 0.65 ± 0.26 mN/m², respectively. Mucoadhesive strength was found to be ranging between 5.75 ± 4.41 and 42.85 ± 3.94 g. Value of release exponent (n) was found to be 0.65 ± 0.22, indicating anomalous drug release behavior from the formulations. Numerical optimization using the desirability approach was employed for developing optimized formulation by setting constraints of the dependent and independent variables. The mucoadhesive tablet formulation composition consisting of 8.58% w/w Eudragit RLPO, 7.02% w/w iron oxide and 7.26% w/w PVP K 30 fulfilled maximum requirements of an optimum formulation with better regulation of the selected constraints.

Conclusions: Eudragit RLPO and iron oxide combination showed high level potential for fabricating gastroretentive as well as mucoadhesive drug delivery systems.     

Formulation and In vitro assessment of sustained release terbutaline sulfate tablet made from binary hydrophilic polymer mixtures

In the present systematic study, a sustained release of terbutaline sulfate tablet (TBS) was developed and optimized by employing the hydrophilic polymers; chitosan and xanthan gum mixed with sodium bicarbonate as a release modifying agent. This formulation was developed using direct compression technology. In vitro release studies indicated rapid swelling and drug release in the initial period of the acid stage from a matrix composed of chitosan and xanthan gum solely. Addition of sodium bicarbonate to the matrix resulted in sustained drug release. Various formulation factors such as polymer to polymer ratio, polymer viscosity and particle size were altered and their effect on dissolution pattern was illustrated. Manufacturing variables such as compression force and lubricant percentage were investigated and found not to influence the drug release profile of the resulted tablets. The release mechanism follows Korsmeyer-Peppas equation with n value indicating non-Fickian diffusion. The release profiles were analyzed using statistical method (one-way ANOVA) and f₂ metric values and found to be similar to the commercial product Bricanyl^®. Reproducible data were obtained when scale-up of the formulation was performed.     

Badam gum: a natural polymer in mucoadhesive drug delivery. Design,optimization, and biopharmaceutical evaluation of badam gum-based metoprolol succinate buccoadhesive tablets

Context: Applicability of natural polymers in pharmaceutical drug delivery.

Objective: The objective of the present investigation was to evaluate the applicability of badam gum (BG) obtained from Terminalia catappa LINN, belongs to the family combretaceae as a buccoadhesive polymer using metoprolol succinate as a model drug.

Methods: Tablets were prepared by wet granulation technique. Compression coating technique was employed for the preparation of unidirectional release buccal tablets using cellulose acetate as an impermeable backing layer.

Results: Muco/buccoadhesive properties of the BG were increased with the increase in the concentration of polymer which was evident form the detachment force measurement, ex vivo residence time, and swelling studies. MBG 2 was found to be the optimized formulation based on drug dissolution studies and bioadhesion studies. FTIR and DSC studies performed on the optimized formulation indicated no drug–polymer interaction. MBG 2 was found to be stable after accelerated stability testing for 6 months as per ICH guidelines. Pharmacokinetic studies of the optimized formulation were performed in six healthy human volunteers in comparison with that of the commercial extended release oral tablet GUDPRESS XL-25 by estimating pharmacokinetic parameters and mean residence time (MRT). It was found that there is a significant increase in the bioavailability of metoprolol succinate from BG formulation which was evident from the high AUC and MRT values compared with the commercial formulation.

Conclusion: The above results clearly indicated that badam gum can be used as a mucoadhesive polymer for buccal drug delivery.     

Development of in situ gel for nasal delivery: design,optimization, in vitro and in vivo evaluation

Abstract

Context: The mucoadhesive gel formulations are helpful to prolong the residence time at the nasal absorption site and thereby facilitate the uptake of drug. Sumatriptan succinate has oral bioavailability of 15% and undergoes hepatic metabolism, hence it is suitable for nasal administration.

Objective: The objective of the investigation was to develop a mucoadhesive in situ gel to improve the bioavailability of the sumatriptan succinate.

Materials and methods: Deacetylated gellan gum was used as gelling agent. In situ gel was formulated by ion activation mechanism in simulated nasal fluid. A 3² factorial design was found suitable to optimize batch. In vivo study was carried out in Spraugue-Dawley rats, and drug was estimated in plasma by UPLC-MS.

Result: The optimized batch showed drug release of 98.57% within 5?h followed by Peppas model of drug release. Ex vivo studies on sheep nasal mucosa showed 93.33% within 5?h. In histopathological study, optimized batch was found to be safe and stable in accelerated stability study for three months. Optimized formulation, F7 has shown absolute bioavailability, which was found to be 164.70%. Drug targeting index for brain tissues was found to be 1.866.

Discussion: Concentration of the gelling polymer was compromised for satisfactory gel strength and an acceptable viscosity. The release depended on viscosity of formulation. Drug targeting index indicates sumatriptan can reach to brain via olfactory pathway.

Conclusion: In situ gel proved to be suitable for administration of sumatriptan succinate through nasal route. The ease of administration coupled with less frequent administration enhances patient compliance.     

Enhancement of dissolution of nystatin from buccoadhesive tablets containing various surfactants and a solid dispersion formulation

Nystatin is commonly employed to treat fungal infections in the mouth. It is not absorbed via the stomach and it will therefore not treat fungal infections in any part of the body other than the mouth. Nystatin buccoadhesive tablets release the drug very slowly due to the poor solubility of nystatin in water and also the presence of polymers with mucoadhesive properties. Therefore, the aim of the present study was to improve drug release from buccoadhesive tablets, while retaining adequate mucoadhesive properties. To this end, a solid dispersion of nystatin: lactose (1:3) was prepared and mixed with xanthan. The effects of hydrophilic surfactants such as cremophor RH40 and Tween 80 on drug release and mucoadhesive properties of nystatin tablets were also investigated as were swelling and erosion indices and strength of bioadhesion in vitro to a biological membrane. The interaction between nystatin and lactose in solid dispersion formulation was investigated by XRPD, FT-IR and DSC. The results showed that a solid dispersion formulation and mucoadhesive tablets containing surfactants led to faster drug release than their simple physical mixtures. Drug release was also faster from a solid dispersion compared to tablets containing surfactants. Swelling and erosion results showed that tablets made of a solid dispersion swelled and eroded faster than a physical mixture formulation. The presence of surfactant slightly increased the degree of swelling and erosion of buccoadhesive tablets.     

Formulation and evaluation of mucoadhesive buccal films impregnated with carvedilol nanosuspension: a potential approach for delivery of drugs having high first-pass metabolism

Abstract

Context: Mucoadhesive buccal films containing three layers (mucoadhesive layer, nanosuspension containing layer and backing membrane) were incorporated with carvedilol nanosuspension.

Objective: Formulation and evaluation of nanosuspension incorporated mucoadhesive buccal films of carvedilol for bioavailability enhancement by avoiding first-pass metabolism.

Methods: Carvedilol-loaded nanosuspension was prepared by a precipitation–ultrasonication method with varying concentrations of the polymer. The formulation was analyzed for size, size distribution, surface charge and morphology. Optimized nanosuspension was incorporated into drug gel layer which was sandwiched between a mucoadhesive layer and a backing layer to form tri-layered buccal films. They were evaluated for their physical, mechanical and bioadhesive parameters followed by in vitro and in vivo studies.

Results and discussion: Nanosuspension showed a negative zeta potential (?17.21?mV) with a diameter of around 495 nm and a polydispersity index of 0.203. Nanosuspension incorporated drug gel layer (62.4% drug loading) was optimized to contain 3% HPMC and 50?mg Carbopol 934P. The mucoadhesive layer and the backing layer were optimized to contain 3% HPMC and 1% ethyl cellulose, respectively. In vitro drug release was 69% and 62.4% in 9?h across synthetic membrane and porcine buccal mucosa, respectively. In vivo studies conducted in rabbit model showed 916% increase in the relative bioavailability in comparison to marketed oral tablet formulation. The C_max and T_max of the prepared formulation increased due to increased surface area of drug and also by-passing hepatic metabolism.

Conclusion: The drug delivery system has been designed as a novel platform for potential buccal delivery of drugs having high first-pass metabolism.     

Design and evaluation of gastroretentive mucoadhesive cephalexin tablets

The aim of this investigation was to develop gastroretentive mucoadhesive tablets of cephalexin, which will retain in the stomach for 10?h. Cephalexin, a first-generation cephalosporin, becomes ionized in intestinal pH because pKa is 4.5 and thus reducing its bioavailability. The various batches were prepared by wet granulation method using variety of mucoadhesive polymers such as hydroxyl propyl methyl cellulose K4M, hydroxyl propyl cellulose, chitosan, carbopol 934P and sodium carboxymethylcellulose and subjected to various evaluation parameters such as mucoadhesive strength, in vitro drug release profile, swelling characteristics and physical properties. It was evident from the study that the formulation containing HPMC K4M and carbopol 934P in combination exhibited maximum mucoadhesive strength of 144.42?gms, in vitro residence time was 8.73?h and in vitro drug release was found to be 75.03% in 10?h with non-Fickian diffusion mechanism. So, the optimized formulation F₂ was further subjected to in vivo retention time in rabbit by X-ray technique, SEM and Accelerated stability studies. Regarding all the properties evaluated, the formulation containing HPMC K4M and carbopol 934P in combination was found to be the best to achieve the aim of this study.     

Buccal films of prednisolone with enhanced bioavailability

Abstract

The conventional formulation of prednisolone is considered to be low in efficacy, primarily on account of their failure in providing and maintaining effective therapeutic drug levels. This study aims to focus on development of a mucoadhesive buccal delivery system with a twofold objective of offering a rapid as well as a prolonged delivery of prednisolone coupled with enhanced therapeutic efficacy. Buccoadhesive films of prednisolone were prepared by solvent-casting method using hydroxyl propyl methyl cellulose (K100), Carbopol 940 and/or Eudragit® NE 40?D. Placebo films possessing the most desirable physicomechanical properties were selected for drug loading. The effect of polymer and its content on film properties, i.e. mucoadhesive strength, swelling and hydration, in vitro drug release was studied. Based on these studies, film F7D was selected for ex vivo permeation across porcine cheek mucosa. The steady state flux of prednisolone across the buccal mucosa was found to be 105.33?±?32.07?µg/cm²/h. A comparative pharmacokinetic study of prepared film (F7D) and oral suspension of prednisolone was conducted. In vivo data of buccal film show greater bioavailability (AUC_0–α: 24.26?±?4.06?µg.h/ml versus 10.65?±?2.15?µg.h/ml) and higher C_max (2.70?±?0.38?µg/ml versus 2.29?±?0.32?µg/ml) value when compared to oral suspension. The data observed from this study highlight the feasibility of the buccal route as a viable option for delivery of prednisolone.     

Development and Evaluation of Microbial Degradation Dependent Compression Coated Secnidazole Tablets for Colonic Delivery

The present paper describes development of a polysaccharide based compression coated tablets of secnidazole for colon delivery. Core tablet containing secnidazole was compression coated with various proportions of guar gum, xanthan gum and chitosan, either alone or in combinations. Drug release studies were performed in simulated gastric fluid (SGF) for 2 h followed by simulated intestinal fluid (SIF, pH 7.4) up to 24 h. Secnidazole release from the prepared formulations was dependent on the type and concentration of polymer used in the formulation. Tablets coating containing either guar gum or xanthan gum showed ~30-40% drug release in 8 h. Further, in vitro dissolution studies of selected formulations performed in the dissolution media with rat caecal contents showed 54.48±0.24 - 60.42±0.16% of drug release. Formulations with single polymer in coating layer were unsuitable for targeting secnidazole release to colon region. Combination of chitosan with guar gum or xanthan gum exhibited control over secnidazole release.     

Development of mucoadhesive floating hollow beads of acyclovir with gastroretentive properties

Abstract

This study aimed at improving the oral bioavailability of acyclovir (ACV) through incorporating it into gastroretentive dosage form based on floating hollow chitosan beads. Hollow chitosan beads were prepared using a solvent free, ionotropic gelation method. The effect of formulation parameters, including chitosan molecular weight and drug concentration, on bead characteristics was studied. The drug containing formulations had yields >70.5?±?0.31%. The entrapment efficiencies for the medium molecular weight chitosan formulations (56.29?±?0.94%–62.75?±?0.86%) was greater than the high molecular weight chitosan formulation (29.21?±?0.89%). The density of all formulations was below that of gastric fluid, the greatest density observed was 0.60?±?0.01?g?cm^?3. Unsurprisingly, the formulations were immediate bouyant to different degrees in both pH 1.2 and pH 6.8 media. In addition, the chitosan beads were all seen to swell in pH 1.2 media and demonstrated mucoadhesive properties. A sustained release profile was observed from the chitosan beads, the developed formulations released drug at slower rates than a marketed ACV oral tablet. The developed system has the dual advantages of being gastroretentive, to increase oral bioavailability and releasing drug in a controlled manner, to reduce the required frequency of administration thereby promoting patient adherence.     

Formulation,evaluation and pharmacokinetics of colon targeted pulsatile system of flurbiprofen

Objective: The intent of the present investigation is to develop colon targeted compression coated flurbiprofen pulsatile release tablets that retard the drug release in the upper gastro intestinal system but progressively release in the colon.

Materials and methods: Flurbiprofen core tablets were prepared by direct compression method and were compression coated with hydroxypropyl methylcellulose and Eudragit S100. The formulation is optimized based on the in vitro drug release study and further evaluated by X-ray imaging and pharmacokinetic studies in healthy humans for colonic delivery.

Results and discussions: The optimized formulation showed negligible drug release (7.26?±?0.05%) in the initial lag period followed by progressive release (99.27?±?0.46%) for 24?h. The X-ray imaging study in human volunteers showed that the tablets reached the colon without disintegrating in the upper gastrointestinal tract. The C_max of colon targeted tablets was 10792.62?ng/mL at T_max 10?h where as in case of immediate release tablets the C_max was 15684.79?ng/mL at T_max 3?h signifies the ability of compression coated tablets to target the colon.

Conclusion: Development of pulsatile release compression coated tablets using combination of time dependent and pH sensitive approaches was suitable to target the flurbiprofen to colon.     

Pharmacokinetics and analgesic effect of ketorolac floating delivery system

Abstract

Objectives: The efficacy of ketorolac tromethamine (KT) floating alginate beads as a drug delivery system for better control of KT release was investigated. The formulation with the highest drug loading, entrapment efficiency, swelling, buoyancy, and in vitro release would be selected for further in vivo analgesic effect in the mice and pharmacokinetics study in rats compared to the tablet dosage form.

Methods: KT floating alginate beads were prepared by extrusion congealing technique. KT in plasma samples was analyzed using a UPLC MS/MS assay.

Results: The percentage yield, drug loading and encapsulation efficiency were increased proportionally with the hydroxypropylmethyl cellulose (HPMC) polymer amount in the KT floating beads. A reverse relationship was observed between HPMC amount in the beads and the KT in vitro release rate. F3-floating beads were selected, due to its better in vitro results (continued floating for >8?h) than others. A longer analgesic effect was observed for F3 in fed mice as compared to the tablets. After F3 administration to rats, the C_max (2.2?±?0.3?µg/ml) was achieved at ～2?h and the decline in KT concentration was slower. F3 showed a significant increase in the AUC (1.89 fold) in rats as compared to the tablets.

Conclusion: KT was successfully formulated as floating beads with prolonged in vitro release extended to a better in vivo characteristic with higher bioavailability in rats. KT in floating beads shows a superior analgesic effect over tablets, especially in fed mice.     

Mucoadhesive buccal film containing ornidazole and dexamethasone for oral ulcers: in vitro and in vivo studies

A bilayered mucoadhesive buccal film containing a combination of ornidazole (OD) and dexamethasone sodium phosphate (DEX) was prepared using solvent casting to treat oral ulcers. Films were systematically evaluated in vitro to obtain the optimum formulation. The therapeutic effects of these films were investigated in the rabbit oral ulcer model and the in vivo release of OD and DEX in the human oral cavity was also evaluated. The backing layer contained ethyl cellulose and an optimal mucoadhesive layer containing both OD and DEX was produced. Films from the optimum formulation were 0.427?±?0.015?mm thick, weighed 55.89?±?0.79?mg, and had a surface pH of 6.34?±?0.01. The drug content of the optimum formulation approximated the theoretical value with good uniformity (2.959?±?0.106?mg/cm² for OD and 0.877?±?0.031?mg/cm² for DEX). The formulation showed favorable swelling characteristics and both drugs were released at >95% after 4?h. Moreover, the compound film had a statistically significant effect on mucosal repair and reduced ulcer inflammation without stimulating the human oral mucosa. C_max of OD in saliva was 37.04?μg/ml and that of DEX was 9.737?μg/ml. Given promising therapeutic effects, the compound film developed here could become a local drug delivery device for treating oral ulcers.     

Statistical modeling,optimization and characterization of solid self-nanoemulsifying drug delivery system of lopinavir using design of experiment

Objective: Lopinavir (LPV), an antiretroviral protease inhibitor shows poor bioavailability because of poor aqueous solubility and extensive hepatic first-pass metabolism. The aim of the present work was to investigate the potential of the solid self-nanoemulsifying drug delivery system (S-SNEDDS) in improving dissolution rate and oral bioavailability of LPV.

Materials and methods: Liquid SNEDDS (L-SNEDDS) of LPV were prepared using Capmul MCM C8, Cremophor RH 40 and propylene glycol and their amounts were optimized by Scheffe’s mixture design. L-SNEDDS formulations were evaluated for different physicochemical and in vitro drug release parameters. S-SNEDDS were prepared by adsorbing L-SNEDDS on Neusilin US2 and characterized for solid-state properties. In vivo bioavailability of S-SNEDDS, marketed Lopinavir?+?Ritonavir (LPV/RTV) formulation and pure LPV was studied in Wistar rats. Stability study of S-SNEDDS was performed as per ICH guidelines.

Results and discussion: Optimized L-SNEDDS obtained by Scheffe design had drug loading 160?±?1.15?mg, globule size 32.9?±?1.45?nm and drug release?>95% within 15?min. Solid state studies suggested the transformation of the crystalline drug to amorphous drug. The size and zeta potential of globules obtained on dilution S-SNEDDS remained similar to L-SNEEDS. In vivo bioavailability study revealed that S-SNEDDS has 2.97 and 1.54-folds higher bioavailability than pure LPV and LPV/RTV formulation, respectively. The optimized S-SNEDDS was found to be stable and had a shelf life of 2.85 years.

Conclusion: The significant increase in drug dissolution and bioavailability by prepared SNEDDS suggest that the developed S-SNEDDS is a useful solid platform for improving oral bioavailability of poorly soluble LPV.     

Development of gastroretentive drug delivery system for cefuroxime axetil: In vitro and in vivo evaluation in human volunteers

The objective of this investigation was to develop the cefuroxime axetil sustained-release floating tablets to prolong the gastric residence time and compare their pharmacokinetic behavior with marketed conventional tablets (Zocef). The floating tablets were developed using polymers like HPMC K4M and HPMC K100M alone, and polymer combination of HPMC K4M and Polyox WSR 303 by effervescent technique. Tablets were prepared by slugging method and evaluated for their physical characteristics, in vitro drug release, and buoyancy lag time. The best formulation (F10) was selected based on in vitro characteristics and used in vivo radiographic and bioavailability studies in healthy human volunteers. All the formulations could sustain drug release for 12 h. The dissolution profiles were subjected to various kinetic release models and it was found that the mechanism of drug release followed Peppas model. The in vivo radiographic studies revealed that the tablets remained in stomach for 225±30 min. Based on in vivo performance, the developed floating tablets showed superior bioavailability than Zocef tablet. Based on in vivo performance significant difference was observed between C_max, t_max, t_1/2, AUC_0–∞, and mean residence time of test and reference (p<0.05). The increase in relative bioavailability of test was 1.61 fold when compared to reference.     

利格列汀双层缓释片的制备及体外释放研究

目的 制备一种新型利格列汀双层缓释片，并考察其体外释放行为。方法 以羟丙基甲基纤维素（hydroxyl propyl methyl cellulose，HPMC）为骨架材料、黄原胶为黏合剂，采用单因素设计筛选处方，进行利格列汀双层缓释片的制备，并绘制处方在pH 6.80介质中的体外溶出曲线；采用常规Ritger-Peppas、Higuchi、一级、零级释放曲线方程进行拟合，分析样品释药原理。结果 经优化后的样品由含药缓释层和含药速释层构成。缓释层由主成分利格列汀3 mg、缓释骨架材料HPMC（型号：K4M及K100M，用量均50 mg）、填充剂微晶纤维素100 mg、凝胶缓释基质黄原胶15 mg、润滑剂硬脂酸镁1 mg组成；速释层由主成分利格列汀2 mg、填充剂微晶纤维素10 mg、崩解剂交联聚乙烯吡咯烷酮15 mg、润滑剂硬脂酸镁1 mg组成。最终结果与零级释放方程匹配度最高，极具相关性，拟合结果r²无限接近于1。结论 成功制得利格列汀双层缓释片，并实现零级释放。     

Design and evaluation of sustained release mucoadhesive film of sumatriptan succinate containing grafted co-polymer as the platform

PurposeThe primary goal of this research is to improve the bioavailability and efficacy of Sumatriptan succinate by incorporating it in the mucoadhesive film for the treatment of migraine. Mucoadhesive film offers an excellent substitute to deliver the drug in the systemic circulation and eliminate the chance of first-pass metabolism.MethodUsing central composite design (CCD), various formulations were created by incorporating polymer, plasticizer, and water, and an optimized preparation was created using statistical screening. The optimization has been performed by applying a 3⁴ factorial method based on dependent variables such as Drug content (%), Swelling index (%), Folding endurance (Number of times), and Mucoadhesive strength (g).ResultsThe actual experimental values obtained were compared with those predicted by the mathematical models. Formulation S9 was selected as an optimized formulation because it showed the lowest standard deviation between predicted and actual values compared to other formulations. In the case of the S9 formulation, approximately 77.12% of the drug was released within 24 h, but initially, it showed burst release. In addition, the in-vitro release of pure drug suspension showed 99.32% drug release within 2 h. That signified that the developed formulation provides sustained release due to presence of grafted co-polymer.ConclusionFormulation holding drug-loaded grafted film showed decent sustained and controlled drug release characteristics compared to a pure drug suspension. S9 formulation showed better results than other formulations in drug content, swelling index, folding endurance, and mucoadhesive strength, which is further used to treat migraine.     

Preparation and pharmacokinetics evaluation of oral self-emulsifying system for poorly water-soluble drug Lornoxicam

Abstract

The present work was performed aiming to develop a new solid self-emulsifying system (SMEDDS) for poorly water-soluble drug Lornoxicam and evaluate the bioavailability in Wister rats by oral gavage. Liquid SMEDDS of Lornoxicam was formulated with Labrafil M 1944 CS as oil phase, Kolliphor HS 15 as a surfactant and Transcutol HP as a cosurfactant after screening various vehicles. The microemulsion system selected from the phase diagram and optimized by central composite design (CCD) response surface method was transformed into solid-SMEDDS (S-SMEDDS) by lyophilization using sucrose as cryoprotectant. The formulations were further characterized by the particle size, poly dispersity index (PDI), self-emulsifying time, zeta potential, transmission electron microscope (TEM), differential scanning calorimeter (DSC), in vitro drug release and in vivo pharmacokinetics. Results of DSC studies confirmed that the drug was incorporated in the S-SMEDDS. The in vitro drug release from Lornoxicam SMEDDS was found to be greatly higher in comparison with that from the commercial tablets. It was indicated that SMEDDS might be effective in reducing the effect of pH variability of Lornoxicam and improving the release performance of Lornoxicam. HPLC system was applied to study the concentration of Lornoxicam in the plasma of the Wister rats after oral administration of Lornoxicam SMEDDS and Lornoxicam commercial tablets. The pharmacokinetics parameters of the rats were C_max 1065.91?±?224.90 and 1855.22?±?748.25?ngmL^?1, T_max were 2.5?±?0.4?h and 1.8?±?0.5?h, and AUC_0～t were 5316.35?±?323.62 and 7758.07?±?241.57?ngmL^?1?h, respectively. Calculated by AUC_0～∞, the relative bioavailability of Lornoxicam S-SMEDDS was 151.69?±?15.32%. It suggested that this S-SMEDDS could be used as a successful oral solid dosage form to improve the solubility and bioavailability of poorly water-soluble drug Lornoxicam as well.