Thermoreversible nanoethosomal gel for the intranasal delivery of Eletriptan hydrobromide

The objective of the current study was to formulate and characterize thermoreversible gel of Eletriptan Hydrobromide for brain targeting via the intranasal route. Ethosomes were prepared by 3² factorial design with two independent variables (concentration of soya lecithin and ethanol) and two response variables [percent entrapment efficiency and vesicle size (nm)] using ethanol injection method. Formulated ethosomes were evaluated for preliminary microscopic examination followed by percent drug entrapment efficiency, vesicle size analysis, zeta potential, polydispersibility index and Transmission electron microscopy (TEM). TEM confirms spherical morphology of ethosomes, whereas Malvern zeta sizer confirms that the vesicle size was in the range of 191 ± 6.55–381.3 ± 61.0 nm. Ethosomes were incorporated in gel using poloxamer 407 and carbopol 934 as thermoreversible and mucoadhesive polymers, respectively. Ethosomal gels were evaluated for their pH, viscosity, mucoadhesive strength, in vitro drug release and ex vivo drug permeation through the sheep nasal mucosa. Mucoadhesive strength and pH was found to be 4400 ± 45 to 5500 ± 78.10 dynes/cm² and 6.0 ± 0.3 to 6.2 ± 0.1, respectively. In-vitro drug release from the optimized ethosomal gel formulation (G4) was found to be almost 100 % and ex vivo permeation of 4980 µg/ml with a permeability coefficient of 11.94 ± 0.04 × 10^?5 cm/s after 24 h. Histopathological study of the nasal mucosa confirmed non-toxic nature of ethosomal gels. Formulated EH loaded ethosomal thermoreversible gel could serve as the better alternative for the brain targeting via the intranasal route which in turn could subsequently improve its bioavailability.     

Pharmacodynamic and pharmacokinetic investigation of cyclodextrin-mediated asenapine maleate in situ nasal gel for improved bioavailability

Asenapine maleate (AM) is used in the treatment of schizophrenia. Its oral and sublingual bioavailability is <2% and 35%, respectively, due to first pass metabolism and poor solubility. To avoid first pass metabolism and to enhance solubility at all nasal pH conditions, thermo-responsive in situ nasal gel containing asenapine maleate-hydroxyl propyl β cyclodextrin inclusion complex (AM-HPβCD) was prepared in the present study. Inclusion complex (1:1 molar ratio) was characterized using UV spectroscopy, FITR and XRD techniques. Selected formulation (F8b) contained a thermo-sensitive polymer poloxamer 407 which formed gel at 23%w/v concentration and a mucoadhesive polymer PVP K 30 (0.3%w/v) in temperature range of 29–34?°c. It was analyzed for pH, clarity, gelation temperature, mucoadhesive strength, gel strength and rheological parameters using Anton paar compact rheometer. This formulation was subjected to in vitro drug diffusion study using the Franz diffusion cell. Maximum % drug diffusion was obtained at the end of 120?min (99.1?±?0.44%w/v). Dissolution in simulated nasal fluid was 92.33?±?0.15%w/v at the end of 120?min. Locomotor activity was improved with nasal gel containing AM-HPβCD as compared to AM and AM-HPβCD oral solution in rats. C_max for nasal gel was found to be more (9?ng/ml) as compared to AM-HPβCD (5.5?ng/mL) and oral standard solution (2?ng/ml). T_max was found to be 1.5?h. AUC and thus bioavailability in rats by nasal route was increased by 2.5 fold.     

Ocular Poloxamer-Based Ciprofloxacin Hydrochloride In Situ Forming Gels

The purpose of this study was to develop poloxamer-based in situ gelling formulations of ciprofloxacin hydrochloride (HCl) aiming at prolonging corneal contact time, controlling drug release, enhancing ocular bioavailability, and increasing patient compliance. The in situ forming gels were prepared using different concentrations of poloxamer 407 (P407) and poloxamer 188 (P188). Mucoadhesives such as hydroxypropylmethyl cellulose (HPMC) or hydroxyethyl cellulose (HEC) were added to the formulations to enhance the gel bioadhesion properties. The prepared formulations were evaluated for their in vitro drug release, sol–gel transition temperature, rheological behavior, and mucoadhesion force. The in vivo antimicrobial efficacy of selected ciprofloxacin HCl in situ gelling formulations was studied on infected rabbit's eyes and compared with that of the marketed conventional eye drops. The gelation temperature of the prepared formulations ranged from 28.00 to 34.03°C. Increasing the concentrations of P407, HPMC, and HEC increased the viscosity and mucoadhesion force of the preparations and decreased the in vitro drug release. Ciprofloxacin HCl in situ forming gel formulae composed of P407/P188/HPMC (18/13/1.5%, wt/wt), and P407/P188/HEC (18/13/0.5%, wt/wt) showed optimum release and mucoadhesion properties and improved ocular bioavailability as evidenced by an enhanced therapeutic response compared with the marketed conventional eye drops.     

Brain-targeted intranasal zaleplon solid dispersion in hydrophilic carrier system; 23 full-factorial design and in vivo determination of GABA neurotransmitter

Intranasal zaleplon solid dispersion was formulated to enhance the solubility, bioavailability and deliver an effective therapy. Zaleplon belongs to Class II drugs, and undergoes extensive first-pass metabolism after oral absorption exhibiting 30% bioavailability. A 2³ full-factorial design was chosen for the investigation of solid dispersion formulations. The effects of different variables include drug to carrier ratio (1:1 and 1:2), carrier type (polyethylene glycol 4000 and poloxamer 407), and preparation method (solvent evaporation and freeze drying) on different dissolution parameters were studied. The dependent variables determined from the in vitro characterization and their constraints were set as follows: minimum mean dissolution time, maximum dissolution efficiency and maximum percentage release. Numerical optimization was performed according to the constraints set based on the utilization of desirability functions. Differential scanning calorimetry, infrared spectroscopy, X-ray diffraction and scanning electron microscopy were performed. Ex vivo estimation of nasal cytotoxicity and assessment of the γ-aminobutyric acid level in plasma and brain 1?h after nasal SD administration in rabbits compared to the oral market product were conducted. The selected ZP-SD, with a desirability 0.9, composed of poloxamer 407 at drug to carrier ratio 1:2 successfully enhanced the bioavailability showing 44% increase in GABA concentration than the marketed tablets.     

Vitamin B12 buccoadhesive tablets: auspicious non-invasive substitute for intra muscular injection: formulation,in vitro and in vivo appraisal

Attempting to prepare a convenient bioavailable formulation of vitamin B₁₂ (cyanocobalamin), 17 tablet formulations were prepared by direct compression. Different concentrations of hydroxypropyl methyl cellulose (HPMC), carbopol 971p (CP971p), and chitosan (Cs) were used. The tablets were characterized for thickness, weight, drug content, hardness, friability, surface pH, in vitro drug release, and mucoadhesion. Kinetic analysis of the release data was conducted. Vitamin B₁₂ bioavailability from the optimized formulations was studied on rabbits by the aid of enzyme-linked immunosorbent assay. Neurotone^® I.M. injection was used for comparison. HPMC (F1-F4), CP971p (F5-F8), and HPMC/CP971p (F12-F15)-based formulations showed acceptable mechanical properties. The formulated tablets showed maximum swelling indices of 232?±?0.13. The surface pH values ranged from 5.3?±?0.03 to 6.6?±?0.02. Bioadhesive force ranged from 66?±?0.6 to 150?±?0.5?mN. Results showed that CP971p-based tablets had superior in vitro drug release, mechanical, and mucoadhesive properties. In vitro release date of selected formulations were fitted well to Peppas model. HPMC/CP971p-based formulations showed bioavailability up to 2.7-folds that of Neurotone^® I.M. injection.     

Development and physico-mechanical characterization of carrageenan and poloxamer-based lyophilized matrix as a potential buccal drug delivery system

Context and objectives: The buccal mucosa presents a unique surface for non-invasive drug delivery and also avoids first-pass metabolism. The objective of this study was the formulation development of polymeric mucoadhesive lyophilized wafers as a matrix for potential buccal drug delivery.

Materials and methods: Differential scanning calorimetry (DSC) was used to develop an optimum freeze-cycle, incorporating an annealing step. The wafers were prepared by lyophilization of gels containing three polymers, κ-carrageenan (CAR 911), poloxamer (P407) and polyethylene glycol 600 (PEG 600). The formulations were characterized using texture analysis (for mechanical and mucoadhesion properties), hydration studies, thermogravimetric analysis (TGA), DSC, X-ray powder diffraction (XRPD) and scanning electron microscopy (SEM).

Results and discussion: DSC showed the eutectic temperature (12.8?°C) of the system where the liquid solution and pure solids both existed at a fixed pressure which helped determine the freeze-annealing cycle at 55?°C for 7?h. Mechanical resistance to compression, hydration and mucoadhesion studies showed that optimized wafers were obtained from aqueous gels containing 2% w/w CAR 911, 4% w/w P407 and 4.4% w/w PEG 600. TGA showed residual water of approximately 1% and SEM showed a porous polymeric network that made ease of hydration possible.

Conclusions: Lyophilized wafers by freeze-drying gels containing 2% w/w CAR 911, 4% w/w P407 and 4.4% w/w PEG 600 with optimum physico-mechanical properties has been achieved.     

Modified drug release of poloxamer matrix by including water-soluble and water-insoluble polymer

Background: The ability of poloxamer 407 to control drug release was investigated along with the effect of incorporation of a second polymer with poloxamer on dissolution behavior. Methods: Tablets made of 30% w/w/ theophylline and 15%, 25%, 50%, or 69% poloxamer were prepared. Additionally, tablets containing mixture of poloxamer with carbomer or hypromellose in a 1:1 ratio and at different total levels (15%, 30%, and 50%) were also tested. Results: Data show that as the level of poloxamer increased, drug release decreased. Formulations containing poloxamer: hypromellose 1:1 at 50% level and formulations containing poloxamer: carbomer 1:1 at 30% level produced controlled release matrices over 24 hours of testing dissolution. The mechanism of drug release follows anomalous relaxation non-Fickian diffusion model. Conclusions: These results suggest that the combination of poloxamer 407 with hypromellose or carbomer is feasible and has potential to offer the formulator control over drug release.     

Ocular poloxamer-based ciprofloxacin hydrochloride in situ forming gels

The purpose of this study was to develop poloxamer-based in situ gelling formulations of ciprofloxacin hydrochloride (HCl) aiming at prolonging corneal contact time, controlling drug release, enhancing ocular bioavailability, and increasing patient compliance. The in situ forming gels were prepared using different concentrations of poloxamer 407 (P407) and poloxamer 188 (P188). Mucoadhesives such as hydroxypropylmethyl cellulose (HPMC) or hydroxyethyl cellulose (HEC) were added to the formulations to enhance the gel bioadhesion properties. The prepared formulations were evaluated for their in vitro drug release, sol-gel transition temperature, rheological behavior, and mucoadhesion force. The in vivo antimicrobial efficacy of selected ciprofloxacin HCl in situ gelling formulations was studied on infected rabbit's eyes and compared with that of the marketed conventional eye drops. The gelation temperature of the prepared formulations ranged from 28.00 to 34.03 degrees C. Increasing the concentrations of P407, HPMC, and HEC increased the viscosity and mucoadhesion force of the preparations and decreased the in vitro drug release. Ciprofloxacin HCl in situ forming gel formulae composed of P407/P188/HPMC (18/13/1.5%, wt/wt), and P407/P188/HEC (18/13/0.5%, wt/wt) showed optimum release and mucoadhesion properties and improved ocular bioavailability as evidenced by an enhanced therapeutic response compared with the marketed conventional eye drops.     

Nanosized nasal emulgel of resveratrol: preparation,optimization, in vitro evaluation and in vivo pharmacokinetic study

Abstract

Nano-emulgel has become one of the most significant controlled release systems, which has the advantages of both gels and nano-emulsions. This work aims at the formulation of nasal nano-emulgel for resveratrol, employing carbopol 934 and poloxamer 407 as the gelling agents. The optimum nano-emulsion was determined through further characterization of the selected system. The nasal nano-emulgel was prepared and tested for the in vitro release, the release kinetics, FTIR, ex vivo permeation, nasal mucosa toxicity, and in vivo pharmacokinetic study. The optimum nano-emulsion consisted of Tween 20, Capryol 90, and Transcutol at a ratio of (54.26: 23.81: 21.93%v/v), and it exhibited transmittance of 100%, resveratrol solubility of 159.9?±?6.4?mg/mL, globule size of 30.65?nm. The in vitro resveratrol released from nano-emulsion and nasal nano-emulgel was 96.17?±?4.43% and 78.53?±?4.7%, respectively. Ex vivo permeation was sustained during 12?h up to 63.95?±?4.7%. The histopathological study demonstrated that the formula is safe and tolerable to the nasal mucosa. C_max and AUC _(0–∞) of resveratrol obtained after nasal administration of nasal nano-emulgel was 2.23 and 8.05 times, respectively. Similarly, T_max was increased up to 3.67?±?0.82?h. The optimized nasal nano-emulgel established intranasal safety and bioavailability enhancement so it is considered as a well-designed system to target the brain.     

Effect of semicrystalline polymers on self-emulsifying solid dispersions of nateglinide: in vitro and in vivo evaluation

This study was undertaken to improve solubility and bioavailability of nateglinide by preparation of stable self-emulsifying solid dispersions (SESDs). The influence of semicrystalline polymers (poloxamer 407, gelucire 50/13) and method of preparation on dissolution behavior, in vivo performance and stability of nateglinide SESDs were investigated. After optimization, SESDs were prepared at 1:5 weight ratio of nateglinide and polymer individually. All the SESDs were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction and scanning electron microscopy. Aqueous solubility of nateglinide was enhanced by 91.82-fold. The SESDs (poloxamer 407-based solid dispersions) achieved rapid and complete drug release (～100% within 45?min) at pH 2. The improved dissolution appeared to be well correlated with the enhanced bioavailability of nateglinide in rabbits. After oral administration of SESDs (poloxamer 407-based solid dispersions), C_max and AUC of nateglinide were increased by ～2.92 and 1.77-folds, respectively, signifying the effectiveness of solid dispersions to improve the bioavailability of nateglinide. Stability during storage was established to show prevention of recrystallization. In conclusion, SESDs with poloxamer 407 in solvent method appeared to be an economic and promising technique to improve the dissolution, bioavailability, and stability of nateglinide.     

Formulation and Characterization of Nanoemulsion-Based Drug Delivery System of Risperidone

Risperidone nanoemulsion (NE) and mucoadhesive NE formulations were successfully prepared by the spontaneous emulsification method (titration method) using Capmul MCM as the oily phase on the basis of solubility studies. The NE formulation containing 8%?oil, 44%?S_mix, 48%?(wt/wt) aqueous phase that displayed an optical transparency of 99.82%, globule size of 15.5?±?2.12 nm, and polydispersity of 0.172?±?0.02 was selected for the incorporation of mucoadhesive components. The mucoadhesive formulation that contained 0.5%?by weight of chitosan displayed highest diffusion coefficient that followed Higuchi model was free from nasal ciliotoxicity and stable for 3 months.     

Development and gamma-scintigraphy study of Hibiscus rosasinensis polysaccharide-based microspheres for nasal drug delivery

Objective: This work describes the application of natural plant polysaccharide as pharmaceutical mucoadhesive excipients in delivery systems to reduce the clearance rate through nasal cavity.

Methods: Novel natural polysaccharide (Hibiscus rosasinensis)-based mucoadhesive microspheres were prepared by using emulsion crosslinking method for the delivery of rizatriptan benzoate (RB) through nasal route. Mucoadhesive microspheres were characterized for different parameters and nasal clearance of technetium-99m (^99mTc)-radiolabeled microspheres was determined by using gamma-scintigraphy.

Results: Their Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) studies showed that the drug was stable during preparation of microspheres. Aerodynamic diameter of microspheres was in the range 13.23?±?1.83–33.57?±?3.69?µm. Change in drug and polysaccharide ratio influenced the mucoadhesion, encapsulation efficiency and in-vitro release property. Scintigraphs taken at regular interval indicate that control solution was cleared rapidly from nasal cavity, whereas microspheres showed slower clearance (p?Conclusion: Natural polysaccharide-based microspheres achieved extended residence by minimizing effect of mucociliary clearance with opportunity of sustained delivery for longer duration.     

In vitro and in vivo evaluation of cubosomal in situ nasal gel containing resveratrol for brain targeting

The aim of this study was to enhance the delivery of resveratrol to the brain through the transnasal route by cubosomes. Cubosomes were prepared using glycerol monooleate and Lutrol F127 by probe sonication method. A 3² full factorial design was used for optimization of cubosomes and batch containing 4% w/v glycerol monooleate and 1.5% w/v of Lutrol F 127 was optimized. The selected cubosomal batch was cubical in shape, having mean particle size 161.5?±?0.12?nm. Entrapment efficiency was found to be 83.08% with zeta potential of –20.9?mV. In vitro release of cubosomal batch showed controlled release of drug profile (67%) up to 24?h. The optimized cubosomal dispersion was dispersed into gelling polymer (poloxamer 407) to form in situ gel for nasal use. The optimal cubosomal gel (containing 12% w/v poloxamer 407) had been subjected to ex-vivo permeation and in vivo biodistribution studies. It showed significantly higher transnasal permeation and better distribution to brain, when compared to the drug solution (i.n.) and drug solution (oral). Finally the cubosomal gel could be considered as a promising carrier for brain targeting of Resveratrol (Res) through transnasal route.     

Development and pharmacokinetic evaluation of alginate-pectin polymeric rafts forming tablets using box behnken design

Abstract

Raft is an emerging drug delivery system, which is suitable for controlled release drug delivery and targeting. The present study aimed to evaluate the physico-chemical properties of raft, in vitro release of pantoprazole sodium sesquihydrate and conduct bioavailability studies. Box behnken design was used with three independent and dependent variables. Independent variables were sodium alginate (X₁), pectin (X₂) and hydroxypropyl methyl cellulose K100M (X₃) while dependent variables were percentage drug release at 2 (Y₂), 4 (Y₄) and 8?h (Y₈). The developed rafts were evaluated by their physical and chemical properties. Fourier transform infrared spectroscopy and differential scanning calorimetry were used to study the chemical interaction and thermal behaviour of drug with polymers. Alginate and pectin contents of R9 formulation were 99.28% and 97.29%, respectively, and acid neutralization capacity was 8.0. R9 formulation showed longer duration of neutralization and nature of raft was absorbent. The raft of R9 formulation showed 98.94% release of PSS at 8?h in simulated gastric fluid. Fourier transform infrared spectroscopy showed no chemical interaction and differential scanning calorimetry indicated endothermic peaks at 250?°C for pantoprazole sodium sesquihydrate. t_max for the test and reference formulations were 8?±?2.345?h and 8?±?2.305?h, respectively. C_max of test and reference formulations were 46.026?±?0.567?µg/mL and 43.026?±?0.567?µg/mL, respectively. AUC_(0-t) of the test and reference formulations were 472.115?±?3.467?µg?×?h/mL and 456.105?±?2.017?µg?×?h/mL, respectively. Raft forming system successfully delivered the drug in controlled manner and improved the bioavailability of drugs.     

Nifedipine in semi-solid formulations for topical use in peripheral vascular disease: preparation,characterization, and permeation assay

Nifedipine (NFD) has been used for the treatment of cutaneous lesions caused by peripheral vascular disease and diabetic ulcers. NFD was formulated at 8% in three semi-solid formulations: Polaxamer 407 Lecithin Organogel (PLO), PLO plus Transcutol^®, and an oil-in-water (o/w) emulsion. In vitro release and permeation tests were carried out using a synthetic (cellulose acetate) or natural membrane (pig ear skin), respectively, mounted in a Franz-type diffusion cell at 37°C in a constant water bath. As a receptor solution, isotonic phosphate buffer at pH 7.4 was used. All samples were analyzed by high-performance liquid chromatography by employing a previously validated method. The drug flow values were 6.126?±?0.288, 4.030?±?0.081, and 6.660?±?0.254 μg/cm²/h for PLO, PLO plus Transcutol^®, and o/w emulsion, respectively. The three formulations did not show significant differences in drug flow, considering p > 0.05. Furthermore, their penetration profiles in both the epidermis and dermis were statistically different. Thus, the incorporation of NFD in PLO, PLO plus Transcutol^®, and o/w emulsion changed the drug thermodynamic activity, as expected. In addition, Transcutol^® increased the solubility of NFD in the formulation and promoted its penetration in both the epidermis and dermis.     

Thermoreversible mucoadhesive in situ nasal gel for treatment of Parkinson’s disease

Abstract

Parkinson’s disease is a degenerative disorder of the central nervous system (CNS). The most obvious symptoms are movement-related such as shaking, rigidity, slowness of movement and difficulty with walking, rigid muscular movements and difficulty in chewing and swallowing especially solid dosage forms. Ropinirole is an anti-Parkinson drug that has low oral bioavailability which is primarily due to first-pass metabolism. The objective of proposed work was to increase bioavailability of ropinirole and avoid patient discomfort by formulating thermoreversible in situ nasal gel. Thermoreversible nasal gels were prepared by cold method using Pluronic F-127 and hydroxy methyl propyl cellulose (HPMC K4M) as gelling agents. Formulations were evaluated for various parameters such as drug content, pH, gelling time, gelling temperature, gel strength, mucoadhesive force, ex vivo diffusion, histological studies and in vivo bioavailability. Formulations displayed gelation at nasal temperature and the gelation time was found to be less than mucociliary clearance time. The nasal residence time was seen to be increased due to mucoadhesion and increased gel strength. The nasal gel formulations showed ex vivo drug release between 56–100% in 5?h. Histological study of sheep nasal mucosa revealed that the gel had a protective effect on the mucosa unlike plain ropinirole which showed evidence of moderate cellular damage. A fivefold increase in bioavailability in brain was observed on nasal administration as compared to IV route. Thermoreversible in situ nasal gel was found to a promising drug delivery for Parkinsonian patients.     

Chlorogenic acid stabilized nanostructured lipid carriers (NLC) of atorvastatin: formulation,design and in vivo evaluation

The present work was aimed at developing an optimized oral nanostructured lipid carrier (NLC) formulation of poorly soluble atorvastatin Ca (AT Ca) and assessing its in vitro release, oral bioavailability and pharmacodynamic activity. In this study, chlorogenic acid, a novel excipient having synergistic cholesterol lowering activity was utilized and explored in NLC formulation development. The drug-loaded NLC formulations were prepared using a high pressure homogenization technique and optimized by the Box-Behnken statistical design using the Design-Expert software. The optimized NLC formulation was composed of oleic acid and stearic acid as lipid phase (0.9% w/v), poloxamer 188 as surfactant (1% w/v) and chlorogenic acid (0.05% w/v). The mean particle size, polydispersity index (PDI) and % drug entrapment efficiency of optimized NLC were 203.56?±?8.57?nm, 0.27?±?0.028 and 83.66?±?5.69, respectively. In vitro release studies showed that the release of drug from optimized NLC formulations were markedly enhanced as compared to solid lipid nanoparticles (SLN) and drug suspension. The plasma concentration time profile of AT Ca in rats showed 3.08- and 4.89-fold increase in relative bioavailability of developed NLC with respect to marketed preparation (ATORVA® tablet) and drug suspension, respectively. Pharmacodynamic study suggested highly significant (**p?0.01) reduction in the cholesterol and triglyceride values by NLC in comparison with ATORVA® tablet. Therefore, the results of in vivo studies demonstrated promising prospects for successful oral delivery of AT Ca by means of its chlorogenic acid integrated NLC.     

Oxycellulose as mucoadhesive polymer in buccal tablets

Background: Oxycellulose (OC) is biodegradable and bioabsorbable cellulose derivative used in medicine to support hemostasis and tissue healing. Recently, its antimicrobial and immunomodulating properties, as well as its potential in modern therapeutic systems as release modifying excipient, drug carrier, and/or mucoadhesive polymer, are widely discussed. Method: To study its last-mentioned characteristics, directly compressed tablets containing 5 mg of cetylpyridinium chloride (CPC) as a model drug and 90 mg of mucoadhesive polymer [oxycellulose sodium (NaOC) alone or in a combination with one of five widely used mucoadhesive polymers] were prepared to ensure 8 hours prolonged release of CPC. Physicochemical and mucoadhesive properties of prepared tablets were evaluated. Results: Based on obtained results, tablets containing OC in combination with hydroxypropylmethylcellulose (Methocel® K100LV) or carboxymethylcellulose sodium showed the best quality parameters (friability < 0.04%, tablet thickness < 2.17 mm, tablet hardness > 85 N, residence time > 256 minutes, mucoadhesive strength > 3.45 mN/mm) and dissolution profiles (more than 81% of CPC released within 8 hours). Conclusion: NaOC embodies excellent compressing, mechanical, and mucoadhesive properties; however, formulation with higher content of NaOC only showed shorter adhesion time (107 ± 7 minutes) and faster drug release (93.66% of CPC released within 2 hours), because of its good solubility in aqueous media.     

Development of a new esomeprazole delayed release gastro-resistant pellet formulation with improved storage stability

This study describes the development of a new esomeprazole (ESO) delayed release gastro-resistant formulation with improved storage stability. A three-step (drug-, sub(seal)- and enteric-) coating process was employed with the aid of a fluid bed coater. Several formulation factors (namely, size and quantity of starting non-pareil sugar spheres, binder quantity during drug-layering, sub(seal)-coating polymer type, and quantity and enteric coating quantity) were evaluated and the whole process was modeled with the aid of feed-forward back-propagation artificial neural networks (ANNs). Results showed that the selection of small-sized starting spheres (45/60 mesh size) leads to pellet agglomeration, while as sub(seal)-coating weight gain increases a reduction in ESO dissolution rate is observed. The enteric-coating applied (Eudragit L30D-55) showed good gastro-resistant performance in both 0.1 N HCl and pH 4.5 media, while immediate release profiles with more than 85% of ESO being released in less than 30?min were obtained. The effect of cellulose-based sub(seal)-coating polymers, (namely, hydroxypropyl cellulose and hydroxypropylmethyl cellulose) on formulation’s storage stability at 40?±?2?°C/75?±?5%RH indicated that only hydroxypropylmethyl cellulose was able to stabilize ESO delayed-release formulations in terms of assay, dissolution, impurities, and gastro-resistance performance. Finally, scanning electron microscopy (SEM) analysis revealed smooth and homogeneous external surface/coating layers in all three levels (drug-, sub(seal)-, and enteric- coating), while x-ray diffraction showed no polymorphic transformations.     

Formulation studies for mirtazapine orally disintegrating tablets

Abstract

Objective: Orally disintegrating tablets (ODTs) recently have gained much attention to fulfill the needs for pediatric, geriatric, and psychiatric patients with dysphagia. Aim of this study was to develop new ODT formulations containing mirtazapine, an antidepressant drug molecule having bitter taste, by using simple and inexpensive preparation methods such as coacervation, direct compression and to compare their characteristics with those of reference product (Remereon SolTab).

Materials and methods: Coacervation method was chosen for taste masking of mirtazapine. In vitro characterization studies such as diameter and thickness, weight variation, tablet hardness, tablet friability and disintegration time were performed on tablet formulations. Wetting time and in vitro dissolution tests of developed ODTs also studied using 900?mL 0.1?N HCl medium, 900?mL pH 6.8 phosphate buffer or 900?mL pH 4.5 acetate buffer at 37?±?0.2?°C as dissolution medium.

Results: Ratio of Eudragit® E-100 was chosen as 6% (w/w) since the dissolution profile of A1 (6% Eudragit® E-100) was found closer to the reference product than A2 (4% Eudragit® E-100) and A3 (8% Eudragit® E-100). Group D, E and F formulations were presented better results in terms of disintegration time. Dissolution results indicated that Group E and F formulations showed optimum properties in all three dissolution media.

Discussion: Formulations D1, D4, D5, E3, E4, F1 and F5 found suitable as ODT formulations due to their favorable disintegration times and dissolution profiles.

Conclusion: Developed mirtazapine ODTs were found promising in terms of showing the similar characteristics to the original formulation.