Faster Drug Release Research Articles

Grafted tamarind kernel polysaccharide based Al3+ cross-linked hydrogel matrices for sustained release of drug in the gastrointestinal milieu

Ionically cross-linked hydrogel serves as an excellent matrix material for the sustained delivery of drugs. Tablets prepared with tamarind kernel polysaccharide (TKP) as the sole matrix material could not provide sustained release of the incorporated drugs. The purpose of the work was to modify TKP and development of ionically cross-linked hydrogel matrix tablets for sustained drug delivery. Grafting of TKP was performed with methacrylic acid (MAA) following the free radical polymerization technique. Hydrogel matrix tablets using Al3+ ion cross-linked grafted TKP were prepared by direct compression method. Al3+ ions were found to considerably influence the erosion, swelling, and paracetamol release from the matrix tablet. Retardation of the erosion, swelling, and paracetamol release was observed with increasing the concentration of Al3+ ions. The hydrogel matrix tablets showed a slow release of drugs in an acidic medium and a relatively faster drug release in an alkaline medium. The optimized formulation having a co-polymer/aluminium hydroxide (Al(OH)3) ratio of 1:1, exhibited sustained drug release action for more than 10 h with lower swelling and erosion of the gel matrix. We conclude that Al3+ ion cross-linked grafted TKP is an excellent matrix material for sustained delivery of drugs in the gastrointestinal milieu.

Novel lipid-based nanocarrier of nitrofurantoin for improved oral bioavailability and reduced variability in absorption

The current research aims to improve oral bioavailability, reduce the variability in absorption, and decrease GI intolerance of Nitrofurantoin (NFT) by presenting in a lipid-based liquid self-nanoemulsifying drug delivery system (L-SNEDDS). L-SNEDDS formulations were developed using a thermosolvency technique. Physicochemical properties including in-vitro drug diffusion were exercised to optimize the formula, further, comparative ex-vivo permeability, in-vitro cell line, in-vitro anti-microbial, and in-vivo pharmacokinetic evaluation of optimized formulation was carried out. Based on the highest saturation solubility, soybean oil, oleoyl polyoxyl-6-glycerides, and diethylene glycol monoethyl ether were selected as oil, surfactant, and co-surfactant, respectively. A Smix ratio of 1:2 was selected based on pseudoternary phase diagrams. The formulation prepared with an equal ratio of oil and Smix exhibited the lowest globule size (59.4 ± 0.8 nm), optimum zeta potential (−21.3 ± 1.1 mV), and faster drug release (95.4 ± 4.2 % in 30 min), and hence was selected for further evaluation. Optimized formulation (SF5) was found stable and showed improved membrane permeability against pure drug suspension (1.84 times) and marketed suspension formulation (1.15 times). SF5 exhibited similar % cell viability and % cell toxicity in Caco-2 cell lines compared to the marketed suspension. However, it showed the highest zone of inhibition against both the gram-negative and gram-positive organisms. The relative bioavailability of NFT-loaded L-SNEDDS was enhanced by 1.46 and 1.55 times compared to the marketed and pure drug, respectively. Thus, it can be concluded that the variability of oral absorption is minimized, and oral bioavailability is improved by the novel lipid-based nanocarrier system of NFT.

Evaluation of Cassia fistula seed galactomannan as tablet-binder in formulation of diclofenac sodium-loaded monolithic matrix tablet

The present study aimed to evaluate Cassia fistula seed galactomannan (CFSG) as a tablet-binder in the formulation of a monolithic matrix tablet using diclofenac sodium as a model drug. Initially, CFSG was extracted and purified from the seeds of the Cassia fistula tree and then screened for phytochemicals. Native CFSG was characterized with polysaccharide content determination, monosaccharide composition analysis, elemental analysis, FTIR, solid-state 13C NMR, molecular weight, zeta potential, DSC, TGA-DTA, XRD, viscosity, pH and surface tension, rheology, SEM and acute oral toxicity study. Prior to formulation, the drug-CFSG compatibility was checked by FTIR, DSC, and XRD. Diclofenac sodium-loaded granules were prepared by the wet granulation method and evaluated for various granule properties. Finally, granules were compressed into tablets and evaluated for binding and other tablet properties. The granules showed to have optimum micromeritic properties. Tablet hardness and friability were found to be approximately 7 kg/m2 and 0.3 %, respectively, which substantiate the excellent binding capacity of CFSG. Other tablet properties were also found to be within the Pharmacopoeial compliance limit. The tablets with a minimum concentration of CFSG (2.5%w/w) as binder showed appreciable mechanical strength and faster drug release, which ratifies CFSG as an alternative tablet binder.

FORMULATION AND EVALUATION OF MOUTH DISSOLVING FILM OF CARIPRAZINE HYDROCHLORIDE

Mouth dissolving film is now a days preferred route of drug administration due to patient compliance. The developed film formulation is a patient-friendly formulation that would be useful for people who have difficulty of swallowing. The results have shown that the HPMC-K4M is good film former and shows bioadhesion property. In combination with PEG-400, it has shown promising fast drug release within 10 min. and good folding endurance. Hence a semi-synthetic cellulose derivative which is affordable and abundantly available can be used as a potential drug release modifier and also used to improve flexibility and processability in the mouth dissolving films. Successful formulation of Cariprazine mouth dissolving films may prevent first pass metabolism to a large possible extent. From the present study it can be concluded that HPMC-K4M based mouth dissolving films of Cariprazine can be successfully prepared with considerable good stability and improved bioavailability Keywords: Mpouth dissolving, Cariprazine, Evaluation

Chitosan/poly (3-hydroxy butyric acid-co-3-hydroxy valeric acid) electrospun nanofibers with cephradine for superficial incisional skin wound infection management

The belated and compromised incisional skin wound healing caused by the invading of methicillin-resistance staphylococcus aureus is a serious problem in clinic. Designing a new therapeutic strategy to inhibit the growth of invading bacteria at post-surgical site might be helpful in fast healing of post-surgical wounds. In this study, we developed cephradine (Ceph) encapsulated chitosan and poly (3-hydroxy butyric acid-co-3-hydroxy valeric acid, (PHBV)) hybrid nanofibers (Ceph-CHP NFs) employing an electrospinning method to revamp the Ceph bioavailability at the post-surgical wound site to prevent the growth of invading bacteria and trigger the wound healing process. The fabricated nanofibers revealed smooth and uniform surface with a diameter range of 160 ± 25 to 190 ± 55 nm, depending on Ceph concentration. Further, the electrospun hybrid nanofibers exhibited a higher entrapment efficiency (EE) and drug loading capacity (DLC) nearly 72.8 ± 5.2 % and 16.5 ± 3.2 %, respectively. Moreover, the Ceph-CHP NFs showed high swelling rate and biodegradation in presence of lysozyme in contrast to blank CHP NFs. Ceph-CHP NFs exhibited fast drug release in initial few hours followed by slow and controlled drug release drug up to 48 h with a constant rate. In-vitro antimicrobial studies indicated the heightened efficacy of Ceph-CHP NFs against MRSA clinical isolates and exhibited no visible cytotoxicity against keratinocytes, HC11 and L929 cells. Lastly, Ceph-CHP NFs showed the enhanced wound healing and bacterial clearance from post-surgical wound compared to Ceph in C57BL/6 mice skin model. Overall, our results showed that Ceph-CHP NFs might be used as a promising wound dressing material for MRSA-infected post-surgical wounds.

Effect of modification of formulation variables on physical characterization of superporouse hydrogel

Superporouse hydrogel (SPH) is widely used and investigated as a gastro retentive drug delivery system to extend drug residence time in the stomach
 
 However, their mechanical strength represents a problem because they need to withstand the peristaltic movement of the stomach. Properties of SPH are widely affected by the materials used for their synthesis. The aim of the research is to study the effect of changing the foaming agent and foam stabilizer amount on physical properties, in particular mechanical strength, and drug release from SPH. Trifluoperazine HCl will be used as model drug in the study.
 SPH formulations was prepared using fixed amount of acrylamide (AM) and polyvinyl alcohol (PVA) as monomers, polyethylene glycol diacrylate (PEGDA) as cross-linker, TRFP as model drug and variable amount of sodium bicarbonate (NaHCO3) as foaming agent, and tween 20 as foam stabilizer. Ammonium persulphate (APS) / tetramethyl ethylenediamine (TEMED) system was used as polymerization initiator. The effect of changing foaming agent and foam stabilizer on mechanical strength, buoyancy, porosity, density, drug release, drug content, swelling ratio, and swelling time was investigated.
 Modifying both factors affected all the physical properties and drug release profile. When tween 20 was increased the mechanical strength, density and floating lag time was increased with a reduction in porosity and drug release. While increasing NaHCO3 reduced mechanical strength, density and floating lag time with increased porosity and faster drug release was observed. Optimum physical properties were observed in formula 2 which had 230 µl of Tween 20 (v/v) and 50 mg of NaHCO3 in which the mechanical strength was 579±0.4, floating lag time 14 min and 80% of the drug was released within 12 hr.
 As a conclusion SPH with improved mechanical strength, physical properties and drug release pattern can be achieved by changing foam stabilizer and foaming agent amount in the formulations.

Tunable Drug Release Rate Using Modular Oral Dosage Forms.

Oral dosage forms with adjustable drug release profiles were prepared using progesterone (PGR) as a poorly-soluble model drug. The dosage forms were made as stack assemblies of functional modules. The modules were made as PGR-carrying HPMC films cut into wafer-like circular pieces. Two types of modules were used in the study; one exhibited comparatively fast drug release and the other slow release. The fast vs. slow release of each type of film utilized resulted from the grade of HPMC used in each case. Drug loading in the assembly was controlled through the total number of modules. By adjusting the proportions of the two types of modules, it is possible to fine-tune the drug release rate of the multi-layer assemblies to a wide range of profiles, bracketed between a high and low end, corresponding to the inherently fastest or slowest release obtainable with the specific materials and procedures employed. This procedure is suitable for adjusting the spring-and-parachute parameters for enhancing/optimizing the bioavailability of poorly-soluble drugs, and for developing patient-centric formulations.

Microfluidics-based PLGA nanoparticles of ratiometric multidrug: From encapsulation and release rates to cytotoxicity in human lens epithelial cells

Multidrug nanomedicine is an effective therapeutic approach for the treatment of chronic diseases and cancers. However, co-encapsulation and release of drug combination at a fixed ratio by nanoparticles, particularly for long acting ocular formulations, remains challenging. Herein, poly (lactic-co-glycolic acid) nanoparticles ratiometrically co-encapsulating hydrophilic dual drugs, mitomycin C and doxorubicin, was obtained (D/M PLGANPs) by combining microfluidics and the Design of Experiments approaches. The formulation variable of lactide-to-glycolide ratios (L/G 50:50, 75:15 and 85:15) was used to achieve fast, medium and slow drug release rates of D/M PLGANPs. The dissolution of D/M PLGANPs in simulated intraocular fluid exhibited sustained release of dual drugs at the fixed ratio over 7 days, and analysis using the Korsmeyer-Peppas model showed mechanism of drug release to be governed by diffusion. More importantly, in human lens epithelial cells, the drug release rate was negatively correlated with drug potency. The slower drug release from D/M PLGANPs led to lower efficacy of drug combination against pathogenesis of cellular migration and proliferation, the key pathogenic processes of capsular opacification after cataract surgery. Compared to fast (L/G 50:50) and medium (L/G 75:15) drug release rate of D/M PLGANPs, the slow release formulation (L/G 85:15) exhibited the least cellular uptake of the dual drugs and the ratio of drug combination was not maintained intracellularly. The present study implicates the potential of using microfluidics for synthesizing polymeric nanoparticles of ratiometric drug combination and highlights the drug release rate as the critical determinant of efficacy for the long-acting nanomedicine design.

PH-sensitive carboxymethyl starch-gelatin coated COF/5-Fu for colon cancer therapy

Owing to the desired structure, recently covalent organic frameworks (COFs) have emerged as one of the more efficient drug-loading platforms. Therefore, in the current study, we constructed COF with a spherical structure as a platform for 5-fluorouracil (5-Fu) loading. The as-synthesized COF showed a larger pore size (∼30.42 nm) than the 5-Fu dimension and a surface area of 230.58 m2/g. With these advantages, the 5-Fu loading percentage on COFs was achieved at ∼93.33 % (COF/5-Fu). However, their imine bond is relatively unstable in harsh acidic conditions. Hence, to prevent the fast drug release at pH 1.2, and considering that the key objective of the frontier work was to construct an oral site-definite controlled drug delivery system, there is an urgent and strong need to cap COF/5-Fu into carboxymethyl starch-gelatin (CMS-Gel) coat (COF/5-Fu@CMS-Gel). Drug release tests showed that the loaded 5-Fu was released highly at pH 7.4, but only 14.11 % of 5-Fu releases occurred at pH 1.2. The structural analyses supported the hypothesis of the successful formation of the prepared samples. The MTT assay showed the biocompatible nature of neat COF@CMS-Gel and its cytotoxic potential after drug loading. All these good properties can guarantee that the COF/5-Fu@CMS-Gel is promising for controlled colon drug delivery.

Preparation and in vitro evaluation of donepezil hydrochloride orodispersible tablets

Objective: The present study was aimed to prepare and evaluate Donepezil HCl Orodispersible tablets (DO-ODTs) using natural and synthetic superdisintegrants to increase patient compliance. Methods: Direct compression was adapted using crospovidone, croscarmellose sodium as synthetic and mucilage isolated from fruits of Abelmoschus esculentus as natural superdisintegrants at different concentrations along with microcrystalline cellulose and aerosil. The powder mixture were subjected for pre and post compression evaluation including FTIR spectroscopy, micromeritic properties, tablet weight variation, hardness, friability, drug content, wetting time, dispersion time, water absorption ration, disintegration time and in vitro drug release. Results: The low SD indicate the drug content was uniform, FTIR suggest no interaction between the drug and the excipients used. The DO-ODTs prepared with croscarmellose at higher concentration shows better in vitro drug release and relative properties than the DO-ODTs prepared with crospovidone and Abelmoschus esculentus. Conclusion: The results of this work reveals that DO-ODTs shows water absorption, dispersion, rapid disintegration time, fast drug release and good hardness, further conclude that DO-ODTs can be efficiently and successfully formulated by direct compression method.

Fabrication of pH-responsive co-delivery system for nano selenium and doxorubicin with PEGylated chitosan: Effect of PEGylation

Drug delivery system has shown multi advantages in cancer treatment, but the complex fabrication process limits their clinical application. This work developed a chitosan-based co-delivery system for doxorubicin and nano selenium. The one-pot co-precipitation process was utilized to form the PEGylated nanoparticles. It was found that the PEGylation might affect the co-precipitation process and result in different nanoparticle sizes and drug release behavior. The PEGylated nanoparticles (Se@DOX/CS-PEG) present a larger diameter (about 230 nm) and higher drug loading capacity (31%). A faster drug release was also observed for PEGylated Se@DOX/CS-PEG nanoparticles and drug release could be completed in 2 h at pH 5.0 while the drug release at pH 7.4 could be limited (<5%, 10 h). In vitro cell experiments confirmed the anti-cancer efficiency and intracellular delivery ability of the co-delivery system. In conclusion, this work presents a novel way to fabricate co-delivery system and may provide more insights into the development of smart drug delivery systems.

Innovative Fibrous Materials Loaded with 5-Nitro-8-hydroxyquinoline via Electrospinning/Electrospraying Demonstrate Antioxidant, Antimicrobial and Anticancer Activities.

A new type of fibrous mat based on a cellulose derivative-cellulose acetate (CA) or CA and water-soluble polymers (polyvinylpyrrolidone, PVP or poly(vinyl alcohol), PVA)-loaded with the model drug 5-nitro-8-hydroxyquinoline (5N) was fabricated via electrospinning or electrospinning in conjunction with electrospraying. Scanning electron microscopy (SEM), X-ray diffraction analysis (XRD), Fourier-transform infrared spectroscopy (FTIR), water contact angle measurements and ultraviolet-visible spectroscopy (UV-Vis) were used for the complex characterization of the obtained novel material. The decoration of CA fibers with a water-soluble polymer containing the drug resulted in the facilitation of wetting and fast drug release. The 5N-containing fibrous material showed antioxidant activity. Moreover, the proposed materials' antibacterial and antifungal properties were tested against S. aureus, E. coli, P. aeruginosa and C. albicans. Well-distinguished, sterile zones with diameters above 3.5 cm were observed around all 5N-containing mats. The mats' cytotoxicity toward HeLa carcinoma cells and normal mouse BALB/c 3T3 fibroblasts was assessed. The 5N-in-CA, PVP,5N-on-(5N-in-CA) and PVA,5N-on-(5N-in-CA) fibrous mats possessed anticancer efficacies and much lower levels of toxicity against normal cells. Therefore, the as-created novel electrospun materials, which are based on polymers loaded with the drug 5N via electrospinning/electrospraying, can potentially be applied for topical wound healing and for local cancer therapy.

A Microstirring Oral Pill for Improving the Glucose-Lowering Effect of Metformin.

Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia due to persistent insulin resistance, resulting in elevated blood glucose levels. Metformin is the most prescribed oral drug for lowering high blood glucose levels in T2DM patients. However, it is poorly absorbed and has low bioavailability. Here, we introduce magnesium-based microstirrers to a metformin-containing pill matrix to enhance the glucose-lowering effect of metformin. The resulting microstirring pill possesses a built-in mixing capability by creating local fluid transport upon interacting with biological fluid to enable fast pill disintegration and drug release along with accelerated metformin delivery. In vivo glucose tolerance testing using a murine model demonstrates that the metformin microstirring pill significantly improves therapeutic efficacy, lowering blood glucose levels after a meal more rapidly compared to a regular metformin pill without active stirring. As a result, the microstirrers allow for dose sparing, providing effective therapeutic efficacy at a lower drug dosage than passive metformin pills. These encouraging results highlight the versatility of this simple yet elegant microstirring pill technology, which enhances drug absorption after gastrointestinal delivery to improve therapeutic efficacy.

Water-responsive 4D printing based on self-assembly of hydrophobic protein "Zein" for the control of degradation rate and drug release.

Four-dimensional (4D) printing is a promising technology that provides solutions for compelling needs in various fields. Most of the reported 4D printed systems are based on the temporal shape transformation of printed subjects. Induction of temporal heterogenicity in functions in addition to shape may extend the scope of 4D printing. Herein, we report a 4D printing approach using plant protein (zein) gel inspired by the amyloid fibrils formation mechanism. The printing of zein gel in a specialized layered-Carbopol supporting bath with different water concentrations in an ethanol-water mixture modulates hydrophobic and hydrogen bonding that causes temporal changes in functions. The part of the construct printed in a supporting bath with higher water content exhibits higher drug loading, faster drug release and degradation than those printed in the supporting bath with lower water content. Tri-segment conduit and butterfly-shaped construct with two asymmetrical wings are printed using this system to evaluate biomedical function as nerve conduit and drug delivery system. 4D printed conduits are also effective as a drug-eluting urethral stent in the porcine model. Overall, this study extends the concept of 4D printing beyond shape transformation and presents an approach of fabricating specialized baths for 4D printing that can also be extended to other materials to obtain 4D printed medical devices with translational potential.

Formulation and Scale-Up of Fast-Dissolving Lumefantrine Nanoparticles for Oral Malaria Therapy

Lumefantrine (LMN) is one of the first-line drugs in the treatment of malaria due to its long circulation half-life, which results in enhanced effectiveness against drug-resistant strains of malaria. However, LMN's therapeutic efficacy is diminished due to its low bioavailability when dosed as a crystalline solid. The goal of this work was to produce low-cost, highly bioavailable, stable LMN powders for oral delivery that would be suitable for global health applications. We report the development of a LMN nanoparticle formulation and the translation of that formulation from laboratory to industrial scale. We applied Flash NanoPrecipitation (FNP) to develop nanoparticles with 90% LMN loading and sizes of 200-260 nm. The integrated process involves nanoparticle formation, concentration by tangential flow ultrafiltration, and then spray drying to obtain a dry powder. The final powders are readily redispersible and stable over accelerated aging conditions (50°C, 75% RH, open vial) for at least 4 weeks and give equivalent and fast drug release kinetics in both simulated fed and fasted state intestinal fluids, making them suitable for pediatric administration. The nanoparticle-based formulations increase the bioavailability of LMN 4.8-fold in vivo when compared to the control crystalline LMN. We describe the translation of the laboratory-scale process at Princeton University to the clinical manufacturing scale at WuXi AppTec.

Design and Evaluation of Dissolvable Microneedles for Treating Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease caused predominantly by immune dysregulation. The global impact of AD continues to increase, making it not only a significant public health issue but also a risk factor for progression into other allergic phenotype disorders. Treatment of moderate-to-severe symptomatic AD involves general skin care, restoration of the skin barrier function, and local anti-inflammatory drug combinations, and may also require systemic therapy, which is often associated with severe adverse effects and is occasionally unsuitable for long-term use. The main objective of this study was to develop a new delivery system for AD treatment based on dissolvable microneedles containing dexamethasone incorporated in a dissolvable polyvinyl alcohol/polyvinylpyrrolidone matrix. SEM imaging of the microneedles showed well-structured arrays comprising pyramidal needles, fast drug release in vitro in Franz diffusion cells, an appropriate mechanical strength recorded with a texture analyzer, and low cytotoxicity. Significant clinical improvements, including in the dermatitis score, spleen weights, and clinical scores, were observed in an AD in vivo model using BALB/c nude mice. Taken together, our results support the hypothesis that microneedle devices loaded with dexamethasone have great potential as a treatment for AD and possibly for other skin conditions as well.

Magnetic two-dimensional Ca-Al layered double hydroxide/Fe3O4@dextran nanocomposites as drug delivery systems

Layered double hydroxides (LDHs) are one of the two-dimensional (2D) anionic clay materials that have received great attention for drug delivery applications due to their high surface-to-volume ratio and drug loading efficiency. In this research, Al-Ca layered double hydroxides (LDHs) were synthesized in situ in presence of Fe3O4@dextran nanoparticles through the co-precipitation method. X-ray diffraction (XRD) studies showed that by increasing the Fe3O4@dextran nanoparticles content, the peaks are broadened due to the intercalation. Field-emission electron microscopy (FESEM) images showed the LDH nanosheets are decorated with Fe3O4@dextran nanoparticles. The saturation magnetization for the sample LDH-Fe3O4@dextran was found to be 13.7 emu/g. The LDH-Fe3O4@dextran sample could load doxorubicin hydrochloride (DOX) with a loading efficiency of 69 %. The in vitro studies showed that the drug release from the synthesized nanocomposite is pH-sensitive. The accumulative release of DOX could reach 59 % in an environment with a pH of 7.4 and 71 % in an environment with a pH of 5.5 within 24 hrs. The synthesized magnetic nano-carrier is promising for its application as a drug delivery nanocarrier with a faster drug release in the tumor microenvironment.

Continuous Manufacturing of Oil in Water (O/W) Emulgel by Extrusion Process

Pharmaceutical industries and drug regulatory agencies are inclining towards continuous manufacturing due to better control over the processing conditions and in view to improve product quality. In the present work, continuous manufacturing of O/W emulgel by melt extrusion process was explored using lidocaine as an active pharmaceutical ingredient. Emulgel was characterized for pH, water activity, globule size distribution, and in vitro release rate. Additionally, effect of temperature (25°C and 60°C) and screw speed (100, 300, and 600rpm) on the globule size and in vitro release rate was studied. Results indicated that at a given temperature, emulgel prepared under screw speed of 300rpm resulted in products with smaller globules and faster drug release.

Radiolabeled Risperidone microSPECT/CT Imaging for Intranasal Implant Studies Development.

The use of intranasal implantable drug delivery systems has many potential advantages for the treatment of different diseases, as they can provide sustained drug delivery, improving patient compliance. We describe a novel proof-of-concept methodological study using intranasal implants with radiolabeled risperidone (RISP) as a model molecule. This novel approach could provide very valuable data for the design and optimization of intranasal implants for sustained drug delivery. RISP was radiolabeled with 125I by solid supported direct halogen electrophilic substitution and added to a poly(lactide-co-glycolide) (PLGA; 75/25 D,L-Lactide/glycolide ratio) solution that was casted on top of 3D-printed silicone molds adapted for intranasal administration to laboratory animals. Implants were intranasally administered to rats, and radiolabeled RISP release followed for 4 weeks by in vivo non-invasive quantitative microSPECT/CT imaging. Percentage release data were compared with in vitro ones using radiolabeled implants containing either 125I-RISP or [125I]INa and also by HPLC measurement of drug release. Implants remained in the nasal cavity for up to a month and were slowly and steadily dissolved. All methods showed a fast release of the lipophilic drug in the first days with a steadier increase to reach a plateau after approximately 5 days. The release of [125I]I- took place at a much slower rate. We herein demonstrate the feasibility of this experimental approach to obtain high-resolution, non-invasive quantitative images of the release of the radiolabeled drug, providing valuable information for improved pharmaceutical development of intranasal implants.

Preparation and characterization of fast-release oral film formulation containing ondansetron hydrochloride solid dispersion

Ondansetron has been widely applied as an antiemetic drug in the treatment or prevention of nausea and vomiting caused by emetic cancer chemotherapy . Fast-release films have the advantages of rapid drug release and improved patients’compliance, especially for the disabled bedridden, the elderly or pediatric patients.The basic film-forming materials were studied through single factor tests and the crystal inhibitors were optimized using solid dispersion technique. The ratio of drug and polymers were optimized by X-ray diffraction (XRD) and Differential Scanning Calorimetry (DSC) which revealed there was no presence of crystal in the optimized solid dispersion. The final film was white thin films and was smooth in surface without obvious bubbles or cracks. Mean weight of each film was 40~50mg. Mean thichness was 60~70μm. Surface pH was 6.4~6.6. The films could release 85% of drug with 1.5min in 0.1mol/L HCl and within 30min in pH6.8PBS. Pharmacolinetic experiment of Ondansetron Hydrochloric solution, marketed films Zuplenz® and the preparation were carried out in rats. As a result, the films of Ondansetron Hydrochloric containing ondansetron solid dispersion had the advantages of fast drug release, improved patient compliance, higher bioavalibility compared to oral solution and the marketed films.