Formulation and characterization of orodispersible film containing diltiazem hydrochloride with taste masked effects.

Orodispersible film (ODF) is a better alternate to oral disintegrating tablets owing to its ease in application and subsequent patient compliance. This study investigates an improvement in physico-mechanical properties and palatability of Diltiazem Hydrochloride (DTZ) by formulating ODF employing solvent casting method. DTZ, used in the treatment of angina and hypertension, undergoes extensive presystemic metabolism and gives an incomplete bioavailability of 35-40%. DTZ also manifests a very bitter taste and after taste. DTZ was formulated into films using different polymer concentrations of Hydroxypropyl methylcellulose ethocel5 and Carboxymethyl cellulose and plasticizer levels of Propylene glycol and Glycerin to screen appropriate polymer-plasticizer combination. Optimized film disintegrated in 10.0±1.53 sec and appeared to be clear and smooth and almost 100% of the drug release was achieved within 4min from the ODF. Film revealed a good mechanical strength with folding endurance of >260, tensile strength of 1.36±0.11 N/mm2 and % elongation of 15.47±0.47%. FTIR and DSC showed compatibility between the drug and polymer. Film demonstrated a slightly sweet taste and after taste as well as an acceptability by the human volunteers. In conclusion DTZ was successfully formulated into film with improved physical properties and taste and could be beneficial to patients with cardiovascular disorders.

Design and Characterization of Agarose/HPMC Buccal Films Bearing Ondansetron HCl In Vitro and In Vivo: Enhancement Using Iontophoretic and Chemical Approaches.

The study was aimed at designing and characterizing the ondansetron hydrochloride (OND) bearing agarose (AG), and hydroxypropyl methyl cellulose (HPMC) mucoadhesive buccal films employing glycerol as a plasticizer. The buccal delivery of ondansetron hydrochloride was remarkably boosted by employing physical (iontophoresis) and chemical enhancement approaches (chemical penetration enhancers). To explore the influence of different formulation components, i.e., agarose, hydroxypropyl methyl cellulose (HPMC), and glycerol on various evaluating parameters, i.e., tensile strength, swelling index, ex vivo mucoadhesion time, and subsequently on in vitro drug release, a D-optimal design was opted. A buccal film bearing OND was mounted on bovine buccal mucosa for ex vivo permeation studies and impact of chemical and physical enhancement techniques on the permeation profile was also analysed. A linear release profile was revealed in in vitro drug release of OND over 60 minutes and outcomes ascertained the direct relationship between HPMC content and in vitro drug release and inverse relationship was depicted by AG content. The FTIR and DSC thermal analysis was executed to determine the physicochemical interactions and results exposed no chemical interactions between drug and polymers. The drug (OND) appeared as tiny crystals on smooth film surface during scanning electron microscopy (SEM) analysis. A notable enhancement in permeation flux, i.e., 761.02 µg/min of OND during ex vivo permeation studies was witnessed after the application of current (0.5-1 mA) without any time lag and with enhancement ratio of 3.107. A time lag of 15 minutes, 19 minutes, and 26 minutes with permeation flux of 475.34 µg/min, 399.35 µg/min, and 244.81 µg/min was observed after chemical enhancer pretreatment with propylene glycol, Tween 80, and passive, respectively. Rabbit was employed as the experimental animal for pharmacokinetic studies (in vivo) and cats for pharmacological activity (in vivo), and the results illustrated the enhanced bioavailablity (2.88 times) in the iontophoresis animal group when compared with the rabbits of control group. Likewise, a remarkable reduction in emesis events was recorded in cats of iontophoresis group. Conclusively, the histopathological examinations on excised buccal mucosa unveiled no severe necrotic or cytopathetic outcomes of current.

Preparation and Characterization of pH-Independent Sustained-Release Tablets Containing Hot Melt Extruded Solid Dispersions of Clarithromycin : Tablets Containing Solid Dispersions of Clarithromycin.

The limited solubility of clarithromycin (CAM), coupled with low bioavailability and rapid elimination, are major shortcomings, needed to be addressed to achieve optimum therapeutic goals. Therefore, sustained-release (SR) tablets containing solid dispersion (SD) granules of CAM were prepared in this study. Initially, SD granules of CAM were prepared by hot melt extrusion (HME) technique using Kollidon VA64 as a hydrophilic carrier. The saturation solubility of SD showed almost 4.5-fold increase as compared to pure CAM in pH 6.8 medium. In vitro drug dissolution data indicated a substantial increase in the dissolution of SD as compared to that of pure CAM. The thermal stability of drug, carrier, and SD at elevated HME temperatures was evident from the results of thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Powder X-ray diffraction (PXRD) data and scanning electron microscope (SEM) images revealed a decrease in the crystallinity and the uniform dispersion of drug, respectively. Moreover, Fourier transformed infrared spectroscopy (FT-IR) data confirmed the formation of hydrogen bond between the carbonyl group of drug and the hydroxyl group of carrier. SD loaded sustained-release (SD-SR) matrix tablets were prepared with hydrophobic polymers (Eudragit RS100 and Eudragit RL100). The pH-independent swelling and permeability of both polymers were responsible for the sustained drug release from SD-SR tablets. Pharmacokinetic (PK) studies suggested a 3.4-fold increase in the relative bioavailability of SD-SR tablets as compared to that of pure CAM.

Solubility and dissolution rate enhancement of ibuprofen by cyclodextrin based carbonate nanosponges.

In the present study nanotechnology approach, i.e., a cyclodextrin (CD) based carbonate nanosponge was used to improve the solubility and dissolution of ibuprofen. Solvent and ultrasound assisted methods were used to prepare nanosponges using two CDs (ß-CD and 2-hydroxypropyl-ß-CD (2HP-ß-CD)) and a cross-linker (CL) diphenyl carbonate (DPC) in varying molar ratios. Nanosponges were investigated for their solubilizing efficiency and phase solubility studies. Structural analysis by Fourier transform infrared (FTIR) and powder X-ray diffraction (PXRD), thermo-analytical characterization by differential scanning calorimetry (DCS), morphology by scanning electron microscopy (SEM). In-vitro drug release followed by in-vivo analgesic and anti-inflammatory studies were performed. 2HP-ß-CD based nanosponges (molar ratio 0.01:0.04) prepared by ultrasound assisted method showed the highest solubilizing efficiency (i.e., 4.28 folds). Stability constant values showed that all complexes were stable. Inclusion complexes of drug was confirmed by PXRD and DSC. SEM images showed porous structures confirming the formation of cross-linked network. Particle size was in the range of 296.8±64 to 611.7±32nm. In-vitro release studies showed enhanced dissolution profile from nanosponge formulation (~94% from I11) as compared to the pure drug (~45% Ibuprofen) in 120min. Significant (p<0.05) extent of pain inhibition and anti-inflammatory activity was observed for nanosponge formulation when compared with the pure drug. CD based carbonate nanosponges with better solubility, enhanced release profile, improved analgesic and anti-inflammatory activity were successfully formulated for ibuprofen.