Extent Of Drug Release Research Articles

Effect of Solutol HS 15 in Solid Dispersions of Pioglitazone Hydrochloride: in vitro and in vivo Evaluation

Poor aqueous solubility and slow dissolution rate adversely affects bioavailability of pioglitazone hydrochloride. This study was undertaken to improve dissolution and bioavailability of pioglitazone hydrochloride through preparation of stable solid dispersions by melting and solvent evaporation method using Solutol HS 15. Solubility of pioglitazone hydrochloride was enhanced by 9 to 49 fold as the drug-carrier ratio was increased in solid dispersions as compared to pure drug. Furthermore, compared to pure drug or physical mixture, solid dispersions significantly improved the dissolution rate and the extent of drug release. Solid dispersions at 1:7 drug:solutol HS 15 weight ratio showed complete and rapid drug release within 15 min at pH 1.2. The Fourier-transform infrared spectrum revealed the chemical compatibility with solutol HS 15. Differential scanning calorimetry and X-ray powder diffraction pattern revealed a change in crystallinity to amorphous state that supported the enhancement of solubility of pioglitazone hydrochloride with Solutol HS 15. In vivo test showed that Solutol HS 15-based solid dispersions showed higher AUC0-t and Cmax, which was ~4 times higher than that of pure pioglitazone (p<0.05) implying solid dispersions could be effective in increasing the bioavailability. In conclusion, solid dispersions with Solutol HS 15 prepared using solvent evaporation method appeared to be a promising technique to improve the dissolution, bioavailability and stability of pioglitazone hydrochloride.

Formulation and Characterization of Fenofibrate Loaded Solid Dispersion with Enhanced Dissolution Profile

Fenofibrate (FF) is an anti-hyperlipidaemic drug belonging to BCS class-II (low solubility, high permeability). Its bioavailability is limited by the dissolution rate. This study was aimed to enhance the rate of dissolution of poorly water soluble drug, FF. Initially, solid dispersions of fenofibrate (SDFs) were formulated with Carplex-80 or PEG-4000 or in combination at various weight ratios and were subjected to dissolution study. On the basis of drug release at various time intervals, the formulation producing maximum drug concentration was evaluated physicochemically using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). It was observed that the peak drug concentration was obtained at 120 min of dissolution by formulation SDF-7, which contains a mixture of Carplex-80 and PEG-4000 at weight ratio 1:5:6 of FF:PEG-4000:Carplex-80, respectively. Thus, the extent of drug release by SDF-7 was maximized by 2.5-fold than that of pure FF. Physicochemical characterization revealed the reason for this increased drug release as a conversion of crystalline FF to amorphous form and ensured the chemical compatibility among FF and carriers. The results specified the significant improvement of FF release using solid dispersion technique.

Effect of the Interaction Between an Ionic Surfactant and Polymer on the Dissolution of a Poorly Soluble Drug

Surfactants are commonly incorporated in conventional and enabled formulations to enhance the rate and extent of dissolution of drugs exhibiting poor aqueous solubility. Generally the interactions between the drug and excipients are systematically evaluated, however, limited attention is paid towards understanding the effect of interaction between functional excipients and its impact on the performance of the product. In the current study, the effect of potential interaction between a nonionic polymer binder, povidone, and anionic surfactant docusate sodium on the rate and extent of dissolution of a drug exhibiting poor aqueous solubility was evaluated by varying the proportions of the binder and the surfactant in the formulation. Potential complexation or aggregation between the excipients was investigated by fluorescence spectroscopy and zeta potential measurements of the aqueous solutions of docusate sodium, povidone, and sodium lauryl sulfate (SLS). The rate and extent of drug release was found to decrease with an increase in the proportion of docusate sodium and povidone in the formulations. Difference in magnitude of surface charge (zeta potential) of docusate sodium in presence of povidone indicated potential surfactant-polymer aggregation during dissolution which was corroborated by CAC/CMC values derived from fluorescence spectroscopic measurements. The decrease in the rate of drug release was attributed to an increase in the viscosity of the microenvironment of dissolving particles due to the interaction of docusate sodium and povidone in the aqueous media during dissolution. These findings highlight the importance of systematic evaluation of the interaction of ionic surfactants with the polymeric components within the formulation to ensure the appropriate selection of the type of surfactant as well as its proportion in the formulation.

Development and in-vitro evaluation of candy based medicated lollipops: a novel system of drug delivery

Lollipops or lozenges are defined as the flavored medicated dosage forms intended to be sucked and held in the mouth or pharynx containing one or more medicaments usually in the sweetened base. Lollipops are commonly used for the purpose of local or systemic effects through the buccal mucosa. Advantages of the lollipop as dosage forms include increase in bioavailability, reduction in dose size, gastric irritation and bypass first metabolism1. Lollipop is designed to improve patient compliance, acceptability, transportation etc2The lollipops were prepared by heating and congealing method in a candy based industry with sucrose base. All the formulations prepared were subjected to various physicochemical parameters like hardness, content uniformity, friability, weight variation etc. Thickness of lollipop ranges from 12-13.2 mm. The hardness of these lollipops ranges between 10-11.5 kg/cm... Results of in-vitro release profile indicated that formulation L3, L6, and L10 were the most promising formulations as the extent of drug release from this formulation was high as compare to other formulations up to 30 mins. The in vitro release of medicated lollipop of ambroxol hcl was found in the release of drug from the lollipop depends on the type and concentration of polymer used. As per all satisfactory evaluation parameters, the batch L3 is found to be optimized batch. The stability studies showed that there was no change in the formulation after 90 days. The medicated lollipops can provide an attractive alternative formulation in the treatment of mucolytics in pediatric patients. Keywords: Amboxol HCl, Lollipops, mucolytic and mucokinetics.

DEVELOPMENT OF ACECLOFENAC OSMOTIC PUMP TABLET FOR CONTROLLED DRUG DELIVERY

Based on monolithic osmotic pump, aceclofenac tablet for controlled drug release system was developed to deliver the drug in a zero order kinetic mode. These osmotic tablets containing 100 mg Aceclofenac were prepared and coated with microporous membrane. The Osmotic Controlled Tablets (OCT) was prepared by using variables like osmogen and osmopolymer. All the tablets were examined and evaluated for physical parameters as well as the in vitro drug release characteristics, studied on USP dissolution apparatus II in 0.1N HCl and phosphate buffer pH 6.8. The drug releases from OCT were found to be dependent on types of osmogens and osmopolymer. All the formulations showed prolonged and controlled aceclofenac release. Sodium chloride based formulation exhibit slightly higher rate and extent of drug release than potassium chloride. Pectin and sodium chloride based tablets offered high push significantly due to higher osmotic pressure.

Fine-tuning the release of molecular guests from mesoporous silicas by controlling the orientation and mobility of surface phenyl substituents

Phenyl-functionalized mesoporous silica materials were used to explore the effect of non-covalent interactions on the release of Ibuprofen into simulated body fluid. Variations in orientation and conformational mobility of the surface phenyl groups were introduced by selecting different structural precursors: 1) a rigid upright orientation was obtained using phenyl groups directly bound to surface Si atoms (Ph-MSN), 2) mobile groups were produced by using ethylene linkers to connect phenyl groups to the surface (PhEt-MSN), and 3) groups co-planar to the surface were obtained by synthesizing a phenylene-bridged periodic mesoporous organosilica (Ph-PMO). The Ibuprofen release profiles from these materials and non-functionalized mesoporous silica nanoparticles (MSN) were analyzed using an adsorption-diffusion model. The model provided kinetic and thermodynamic parameters that evidenced fundamental differences in drug-surface interactions between the materials. All phenyl-bearing materials show lower Ibuprofen initial release rates than bare MSN. The conformationally locked Ph-MSN and Ph-PMO have stronger interactions with the drug (negative ΔG of adsorption) than the flexible PhEt-MSN and bare MSN (positive ΔG of adsorption). These differences in strength of adsorption are consistent with differences between interaction geometries obtained from DFT calculations. B3LYP-D3-optimized models show that π-π interactions contribute more to drug adsorption than H-bonding with silanol groups. The results suggest that the type and geometry of interactions control the kinetics and extent of drug release, and should therefore serve as a guide to design new drug delivery systems with precise release behaviors customized to any desired target.

Comparative Evaluation and Optimization of Film Coating Formulation Variables and Delayed Release Properties of Three Enteric Polymers on Diclofenac Sodium Core Tablets

Enteric coatings present surfaces that have low permeability in the low pH environments of the stomach and release drug from the underlying core when they reach more neutral to alkaline environments of the intestinal milieu. However, the degree of ester substitution in the polymers, resulting in varied pH/dissolution behaviour, affects the rate and extent of drug release, the suitability of methods to be used and the overall cost of medication. In this study, hydroxypropyl methylcellulose phthalate (HPMCP) and two polymethacrylates, Wangit L30D-55® and Wangit L-100® were investigated for their enteric coating properties using diclofenac sodium tablets as core. Both polymers showed acid protective effect at the weight gain of 6%. Polymethacrylate based coatings showed somewhat better surface characteristics and drug release properties than HPMCP. The coating performance of the polymers was found to be better with lower and medium concentration of plasticizer to polymer ratio. The in vitro drug release profiles of the polymethacrylates showed cumulative drug release of 1.72% and 1.69% in 0.1 N HCl over 2 h of release study and 79.5% and 76.1% over 45 min in phosphate buffer pH 6.8, respectively. According to f2 test, the Wangit L30D-55® and Wangit L-100® coated tablets were similar to the two most commonly marketed products of diclofenac sodium 50 mg with f2 values of 66.66 and 70.88, respectively, for Marketed Product-1 (DilcoDenk®) and 59.9 and 58.74 for Marketed Product-2 (Remethan®). The results of the study showed that the polymethacrylates provide better tablet coating properties.Keywords: enteric coating, hydroxypropyl methylcellulose phthalate, polymethacrylates, diclofenac sodium, optimization

Development of solid SEDDS, VII: Effect of pore size of silica on drug release from adsorbed self-emulsifying lipid-based formulations

PurposeLipid-based self-emulsifying drug delivery systems (SEDDS) are usually liquids, and they can be converted into solid dosage forms by adsorbing onto silicates. However, most commercially available silicates are mesoporous with small pore sizes of 1 to 50nm that lead to incomplete emulsification of SEDDS inside the pores and thus incomplete drug release. The objective of this study was to investigate the impact of silica pore size on the extent of drug release from SEDDS solidified by adsorbing onto macroporous silicas with different pore sizes. MethodsSilicas with average pore sizes of approx. 150nm, 500nm and 5μm were synthesized using the colloidal crystal templating method. A model poorly water-soluble drug, probucol, was dissolved in liquid SEDDS containing different lipid to surfactant ratios, and the formulations were then adsorbed onto equal weights of silicas (1:1 w/w ratio). Drug release from freshly prepared formulations and after storing at 40°C/60% RH for up to 6months was studied using a modified USP type 2 method with mini paddles and 50mL of 0.01M HCl (pH~2) at 37°C. Drug release was also studied similarly from silicas that were precoated with PVP K-30 at 5, 10, 20 and 30% w/w levels before adsorption of SEDDS. ResultsFreshly prepared formulations containing relatively higher lipid:surfactant ratio of 7:3% w/w exhibited 17, 40 and 60% drug release from uncoated (neat) silicas with pore sizes of 150nm, 500nm and 5μm, respectively, while the more hydrophilic formulations containing 3:7 w/w lipid:surfactant ratio had, respectively, 50, 65 and 85% drug release. No decrease in drug release was observed when the formulations were exposed to 40°C/60% RH for up to 6months. When the silicas were precoated with 20% PVP, the drug release was almost complete (>80%), which remained unchanged even after 6months of storage irrespective of the composition of adsorbed liquid SEDDS. ConclusionsBoth pore size and composition of SEDDS had major impacts on drug release from silicas. Increased drug release was observed with the increase in pore size of silicas and hydrophilicity of formulations. Since the silicas synthesized were macroporous with no mesopores present, there was no decrease in drug release upon storage. Complete drug release was observed when silicas were precoated with PVP as it increased the penetration of water into the pores.

Drug release studies from lipid nanoparticles in physiological media by a new DSC method

Lipid nanoparticles are an interesting parenteral delivery system for poorly water-soluble drugs. In order to approach physiological conditions when conducting release studies from such systems the release media should preferentially contain lipophilic acceptor compartments such as lipoproteins or other colloidal lipophilic components. In practice, drug release studies under such close to physiological conditions may be complicated by the small size of lipid nanoparticles, which is in the same range as that of the potential acceptor particles. This study describes a novel differential scanning calorimetry (DSC) method for drug release measurements which works without separation of donor and acceptor particles. The technique is based on measuring the crystallization temperature of trimyristin nanoparticles by DSC. The crystallization temperature of the nanoparticles decreases proportionally with the amount of active ingredient incorporated and thus increases as a result of drug release. Liquid trimyristin nanoparticles loaded with fenofibrate, orlistat, tocopherol acetate and ubidecarenone were studied in three different release media with increasing complexity and comparability to physiological conditions: a rapeseed oil nanoemulsion, porcine serum and porcine blood. Using the new method, a correlation between release behavior and drug lipophilicity was observed: the higher the logP value of the drug, the slower the release. The extent of drug release was influenced by partition equilibrium as indicated by increased drug release in the rapeseed oil nanoemulsion compared to porcine serum and blood.

In Situ Preparation of Magnetic Fe3 O4 Nanoparticles in Presence of PLGA and PVA as Magnetite Nanocarrier for Targeted Drug Delivery

Introduction: Drug targeting represents an interesting motivation to prevent side effects and increase doxorubicin cytotoxicity. Magnetic nanoparticles offer new opportunities for developing effective drug delivery systems because they are feasible to produce characterize and specifically tailor their functional properties for drug delivery applications. To improve their stability and biocompatibility, the Fe3O4 nanoparticles are often modified with surfactants or polymers. Materials and Methods: In the present work, a nanocomposite was synthesized via in situ preparation of Fe3 O4 nanoparticles inside poly lactic glycolic acid and poly vinyl alcohol. The anticancer drug of doxorubicin was loaded on the synthesized nanocomposite in order to targeted drug delivery technique. The nanostructures were characterized by FT-IR, SEM, VSM and XRD techniques. The in vitro drug release from synthesized nanocomposite was investigated as nanocarrier in 2 different pHs (equal blood and tumor environments) at 37° C and extent of drug release was calculated by UV-Vis spectrophotometer. Results: In vitro drug release experiments showed that the doxorubicin release at pH=6.0 was promisingly more and faster than pH=7.4. The fitted equation of release curves was corresponded to Peppas model. Conclusion: All these results together suggest that the DOXloaded nanocarrier may serve as a promising magnetic targeting therapy for the treatment of tumor cells.

Controlled drug release from lung-targeted nanocarriers via chemically mediated shell permeabilisation

Nanocarriers can aid therapeutic agent administration to the lung, but controlling drug delivery from these systems after deposition in the airways can be problematic. The aim of this study was to evaluate if chemically mediated shell permeabilisation could help manipulate the rate and extent of nanocarrier drug release. Rifampicin was loaded into lipid shell (loading efficiency 41.0±11.4%, size 50nm) and polymer shell nanocarriers (loading efficiency 25.9±2.3%, size 250nm). The drug release at pH 7.4 (lung epithelial pH) and 4.2 (macrophage endosomal pH) with and without the chemical permeabilisers (Pluronic L62D − lipid nanocarriers; H+- polymer nanocarriers) was then tested. At pH 7.4 the presence of the permeabilisers increased nanocarrier drug release rate (from 3.2μg/h to 6.8μg/h for lipid shell nanocarriers, 2.3μg/h to 3.4μg/h for polymer shell nanocarriers) and drug release extent (from 50% to 80% for lipid shell nanocarriers, from 45% to 76% for polymer shell nanocarriers). These effects were accompanied by lipid nanocarrier distension (from 50 to 240nm) and polymer shell hydrolysis. At pH 4.2 the polymer nanocarriers did not respond to the permeabiliser, but the lipid nanocarrier maintained a robust drug release enhancement response and hence they demonstrated that the manipulation of controlled drug release from lung-targeted nanocarriers was possible through chemically mediated shell permeabilisation.

Design, preparation, and in vitro characterization of a trimodally-targeted nanomagnetic onco-theranostic system for cancer diagnosis and therapy

In this study, the aim was to introduce and characterize a new trimodally-targeted nanomagnetic onco-theranostic system for simultaneous early diagnosis and efficient treatment of cancer. The onco-theranostic system was designed as it could target the tumor site through three targeting approach, i.e. magnetic, folic acid receptor, and pH sensitivity, and concurrently, due to the presence of superparamagnetic iron oxide nanoparticles (SPIONs) with super paramagnetic characteristics could be useful as MRI contrast agent for early cancer diagnosis. To achieve this goal, SPIONs were coated with chitosan and folic acid-conjugated chitosan via ionic gelation method in order to obtain non-targeted nanomagnetic onco-diagnostic (NT/NOD) and targeted nanomagnetic onco-diagnostic (T/NOD) systems. Finally, doxorubicin was loaded successfully into NT/NOD and T/NOD in order to obtain nanomagnetic onco-theranostic (NT/NOT) and targeted nanomagnetic onco-theranostic (T/NOT) systems. The entrapment efficiency and drug loading of T/NOT was determined to be 62.33±5.20% and 10.26±1.36%, respectively. MTT assay revealed that all systems were biocompatible within the concentration range investigated. Also, the T/NOT system showed the lowest IC50 comparing with free doxorubicin and NT/NOT system. In addition, uptake studies and competitive inhibition study verified the folate receptor mediated endocytosis of targeted system by MCF-7 as a folate receptor-positive cell line. The finding revealed that the extent of drug release from theranostic systems was pH-sensitive as it was higher at acidic media compared to that of in the neutral condition. Finally, T2-weighted phantom images, with an acceptable and dose-dependent resolution, proved the potential of T/NOT system as promising T2 MR contrast agent for diagnostic purpose. These finding proved that the prepared T/NOT system have great potential as a novel tumor-targeting nanotheranostic agent for simultaneous MRI imaging and treatment of folate receptor-positive cancers. Further studies are needed to test their behavior in vivo.

Fine tuning of the pH-sensitivity of laponite–doxorubicin nanohybrids by polyelectrolyte multilayer coating

Despite the wide research done in the field, the development of advanced drug delivery systems with improved drug delivery properties and effective anticancer capability still remains a great challenge. Based on previous work that showed the potentialities of the nanoclay Laponite as a pH-sensitive doxorubicin (Dox) delivery vehicle, herein we report a simple method to modulate its extent of drug release at different pH values. This was achieved by alternate deposition of cationic poly(allylamine) hydrochloride and anionic poly(sodium styrene sulfonate) (PAH/PSS) polyelectrolytes over the surface of Dox-loaded Laponite nanoparticles using the electrostatic layer-by-layer (LbL) self-assembly approach. The successful formation of polyelectrolyte multilayer-coated Dox/Laponite systems was confirmed by Dynamic Light Scattering and zeta potential measurements. Systematic studies were performed to evaluate their drug release profiles and anticancer efficiency. Our results showed that the presence of the polyelectrolyte multilayers improved the sustained release properties of Laponite and allowed a fine tuning of the extension of drug release at neutral and acidic pH values. The cytotoxicity presented by polyelectrolyte multilayer-coated Dox/Laponite systems towards MCF-7 cells was in accordance with the drug delivery profiles. Furthermore, cellular uptake studies revealed that polyelectrolyte multilayer-coated Dox/Laponite nanoparticles can be effectively internalized by cells conducting to Dox accumulation in cell nucleus.

Formulation and Evaluation of Fixed Dose Combination Suppositories Containing Stavudine, Lamivudine and Nevirapine for Pediatric Applications

Suppositories are the convenient way of administering drugs in infants. In view of the lack of suitable pediatric antiretroviral formulations in the market, suppositories containing fixed dose combination (FDC) of stavudine, lamivudine and nevirapine (SLN) were developed to allow administration of the correct weight-related dose in pediatric HIV patients as recommended by WHO. Suppositories containing 10 mg of stavudine, 40 mg of lamivudine and 70 mg of nevirapine were prepared by the fusion method using Witepsol H15 semi-synthetic suppository base. All the prepared suppositories were evaluated for various physical parameters like weight variation, melting point, drug content and hardness. The rate and extent of drug release was evaluated using USP apparatus I and samples were analyzed by a validated UV-multicomponent method. The use of surfactants significantly increased the drug release from formulations manufactured with Witepsol H 15 fatty base. The development of pediatric fixed-dose combination formulations represent a new era and mark an important milestone for children living with HIV/AIDS.

Development and characterization of sustain release gastro retentive floating microsphere of diltiazem hydrochloride for the treatment of hypertension

Gastroretentive drug delivery systems are the systems, which are retained in the stomach for a longer period and thereby improve the bio‐availability of drugs. Diltiazem hydrochloride (DTZ HCl), is a calcium channel blocker, an antihypertension and antianginal drug, DTZ HCl undergoes an extensive biotransformation, mainly through cytochrome P‐450 CYP3A, which results in <4% of its oral dose being excreted unchanged in urine. Suffers from poor bio‐availability (~30–40%) owing to an important first pass metabolism. It has an elimination half‐life of 3.5 h and an absorption zone from the upper intestinal tract. Thus, the present work is aimed to formulate sustain release floating microsphere of DTZ HCl for gastroretentive drug delivery system. Floating microsphere were prepared using nonaqueous solvent evaporation method using polycarbonate, chitosan, ethyl cellulose, hydroxypropyl methycellulose and acrycoat as materials in various quantities, in varying ratio to formulate 20 formulations of the floating microsphere. Observations of all formulations for physical characterization had shown that, all of them comply with the specification of official pharmacopoeias and/or standard reference. It was observed that microsphere of batch F3 followed the results obtained, it was concluded that the formulation 98.72% F3 is the best formulations as the extent of drug release was found to be around 99.81% at the desired time 12 h. Key words: Diltiazem hydrochloride, floating microsphere, in vitro buoyancy studies, swelling index

PH-Triggered Magnetic-Chitosan Nanogels (MCNs) For Doxorubicin Delivery: Physically vs. Chemically Cross Linking Approach.

This paper evaluates the impact of cross linking strategy on the characteristics of magnetic chitosan nanogels (MCNs) as targeted drug delivery system for doxorubicin. Sodium tripolyphosphate (TPP) and glutaraldehyde were used as physical (electrostatic) and chemical (covalent binding) cross-linker agents, respectively. MCNs were characterized by means of X-ray diffraction (XRD), Scanning electron microscopy (SEM), fourier transform infrared (FT-IR) spectroscopy and vibrating sample magnetometer (VSM). Scanning electron microscopy (SEM) indicated the formation of spherical nanostructures with the final average particle size of around 35-40 nm. The finding proved the superparamagnetic properties of the MCNs with relatively high-magnetization values which indicate that the MCNs were enough sensitive to external magnetic fields as a magnetic drug carrier. To understand the differences between the drug delivery properties of chemically and physically cross linked MCNs, the drug release studies were also conducted. Altogether, the results of this study clearly indicate that, however, both MCNs exhibited sustained drug release behaviour, the chemically cross linked MCNs provided enhanced controlled drug release characteristics in comparison to physically cross linked MCNs. Besides, according to the drug release behaviour of MCNs in buffer solutions in two different medium with the pH values of 5.3 and 7.4, it was clear that both nanoparticles exhibited pH sensitivity where the extent of drug release in the acidic media was significantly higher than neutral media. It can be concluded that chemically cross linked MCNs may serve as an ideal carrier for stimuli-triggered and controlled anticancer drug delivery.

Calcium ion modulates protein release from chitosan-hyaluronic acid poly electrolyte gel

Polyelectrolyte complex (PEC) of chitosan (CH) and hyaluronic acid (HA) are widely used for skin, cartilage, and bone tissue engineering. However, no reports are seen on their response at high ionic media, like increased Ca2+ where they are likely to be exposed in the form of bone constructs and the influence of these ions on modulating the release of incorporated entities such as drugs and growth factors. Here, we prepared freeze dried scaffolds of PEC of CH and HA (CH-HA) and characterized them by FTIR, TGA, SEM, and ESEM. FITC conjugated BSA, designated as FA, was incorporated into the PEC to study the release properties in response to Ca2+. The swellability of CH-HA and the extent of drug release from the matrix, FA loaded CH-HA was studied in deionised water and aqueous Na+ and Ca2+ solutions. Swelling and drug release were high for the matrix in aqueous Ca2+ whereas it was remarkably low in water and Na+. Drug released was found to increase with concentrations of Ca2+ (0.02–1.0M) indicating that CH-HA is a promising matrix for Ca2+ responsive delivery of agents to accelerate healing of bone cracks, which is known to release high amount of Ca2+. POLYM. ENG. SCI., 55:2089–2097, 2015. © 2015 Society of Plastics Engineers

In-vitro characterisation of a novel celecoxib microbead formulation for the treatment and prevention of colorectal cancer.

Colorectal cancer (CRC) is a life-threatening disease that can develop as a consequence of a sustained chronic inflammatory pathology of the colon. Although not devoid of side effects, the anti-inflammatory drug celecoxib (CLX) has been shown to exert protective effects in CRC therapy. The purpose of this study was to develop and characterise a novel CLX microbead formulation suitable for use in the treatment and prevention of CRC, which has the potential to minimise the side effects associated with CLX. The study involved the assessment of the effectiveness of CLX formulations in an in-vitro cell model (HT29 cells) and a comparison of these effects to that of the marketed CLX product, Celebrex. Liquid CLX formulations were developed as precursors to microbead formulations. The effect of liquid CLX formulations on HT29 cell viability (MTT and flow cytometry apoptotic assays) and motility (scratch wound assay) were assessed and compared with the effect of Celebrex. A correlation between the in-vitro dissolution performance of the formulations and the effect in the cell model was also explored. Liquid CLX formulations were translated into an optimised CLX microbead formulation, and a colonic targeted sustained release coat (Surelease) was applied to the beads with the aim of producing a formulation for a future in-vivo study to compare the effect of the coated CLX microbeads versus Celebrex in the attenuation of CRC tumours and inflammation in a CRC murine model. The production of CLX microbeads was scaled-up using vibrating-jet encapsulation technology to allow for the development of an optimised dissolution profile to enable colonic release. In-vitro cell viability and motility were shown to be significantly reduced after treatment with CLX liquid formulations relative to the control, whereas the results for treatment with Celebrex were comparable with the control. Dissolution experiments and correlation analysis demonstrated that the formulations that showed a greater extent of drug release had reduced cell viability and motility. The CLX liquid formulations were translated into colon-targeted CLX microbeads suitable for use in a future in-vivo mouse study. These results represent a significant step forward in the chemopreventative treatment of CRC using CLX, as the microbead formulation developed suggests the possibility of presenting CLX in a format that has the potential to minimise gastrointestinal and cardiovascular side effects.

Fabrication of a novel scaffold of clotrimazole-microemulsion-containing nanofibers using an electrospinning process for oral candidiasis applications

Clotrimazole (CZ)-loaded microemulsion-containing nanofiber mats were developed as an alternative for oral candidiasis applications. The microemulsion was composed of oleic acid (O), Tween 80 (T80), and a co-surfactant such as benzyl alcohol (BzOH), ethyl alcohol (EtOH) or isopropyl alcohol (IPA). The nanofiber mats were obtained by electrospinning a blended solution of a CZ-loaded microemulsion and a mixed polymer solution of 2% (w/v) chitosan (CS) and 10% (w/v) polyvinyl alcohol (PVA) at a weight ratio of 30:70. The nanofiber mats were characterized using various analytical techniques. The entrapment efficiency, drug release, antifungal activity and cytotoxicity were investigated. The average diameter of the nanofiber mats was in the range of 105.91–125.56nm. The differential scanning calorimetry (DSC) and powder X-ray diffractometry (PXRD) results revealed the amorphous state of the CZ-loaded microemulsions incorporated into the nanofiber mats. The entrapment efficiency of CZ in the mats was approximately 72.58–98.10%, depended on the microemulsion formulation. The release experiment demonstrated different CZ release characteristics from nanofiber mats prepared using different CZ-loaded microemulsions. The extent of drug release from the fiber mats at 4h was approximately 64.81–74.15%. The release kinetics appeared to follow Higuchi's model. In comparison with CZ lozenges (10mg), the nanofiber mats exhibited more rapid killing activity. Moreover, the nanofiber mats demonstrated desirable mucoadhesive properties and were safe for 2h. Therefore, the nanofiber mats have the potential to be promising candidates for oral candidiasis applications.

Evaluation of the Binding Effect of Local Gum of &lt;i&gt;Boswellia papyrifera&lt;/i&gt; in Paracetamol Granules and Tablet Formulations

Boswellia papyrifera is one of the chief gum resin producing tree species in Ethiopia. Frankincense harvested from it is the most widely traded one. Frankincense is used for a variety of purposes from traditional medicine to industries such as pharmaceutical, perfume and food industries. In this work, B. papyrifera gum has been evaluated for its binding effect in paracetamol granules and tablet formulations in comparison with the commonly used binders, Acacia BP and PVP K-30. Some physicochemical properties of the extracted gum indicated that the gum exhibited solubility in water, absence of tannin and slightly acidic pH. The loss on drying and ash value were well within the official limits. Paracetamol granules were prepared using different proportions of B. papyrifera gum (BPA), Acacia BP (ACA) and PVP K-30 by wet granulation method. The granules prepared with the binders exhibited optimum moisture content, good flow properties and compressibility. Percent of fines decreased with increasing binder concentration. Increase in binder concentration led to an increase in crushing strength, decrease in friability and increase in disintegration time of the tablets which were observed in all the three binders. Paracetamol tablets prepared with 2% w/w of BPA and ACA failed to comply with the specification for the friability test (> 1%). All concentrations of PVP and 2 to 6% w/w concentrations of ACA and BPA met the BP specification for disintegration. At 2% w/w to 6% w/w binder levels, there were no significant differences in the extent of drug release among the binders in 30 min. All the batches of ACA, BPA and PVP, except at 8% of BPA, complied with the specification which states that the quantity of drug released should not be less than 80% of the labeled amount of paracetamol in 30 min. From the foregoing, it can be concluded that the gum extract of B. papyrifera oleo-gum resin could be explored as an alternative excipient for its binder effect in granule and tablet formulations. Keywords: Boswellia papyrifera , natural gum, paracetamol, wet granulation, tablet binder