Eudragit Microcapsules of Nifedipine and Its Dispersions in HPMC-MCC: Physicochemical Characterization and Drug Release Studies

Abstract

Nifedipine and its solid dispersions in hydroxypropyl methyl cellulose-microcrystalline cellulose (HPMC-MCC) were microencapsulated with Eudragit RL PM by an emulsion solvent evaporation method. The microcapsules are spherical, discrete, free flowing, and covered with a continuous coating of the polymer. XRD and DTA indicated the presence of nifedipine in solution form in the solid dispersions and their microcapsules. No chemical interaction between nifedipine and excipients in the microcapsules was observed. Nifedipine as such and its microcapsules gave very slow release because of its highly crystalline nature and poor solubility. Solid dispersion in HPMC-MCC gave fast and rapid dissolution of nifedipine. When these solid dispersions were microencapsulated a slow, controlled, and complete release over a period of 12 hr was observed from the resulting microcapsules. Drug release depended on the proportion of HPMC-MCC in the solid dispersion used as a core, coat, core ratio, and size of the microcapsules. Release was independent of pH and ionic strength. Drug release was governed by diffusion rate and followed first-order kinetics.     

Chitosan based mucoadhesive nanoparticles of ketoconazole for bioavailability enhancement: formulation,optimization, in vitro and ex vivo evaluation

Purpose: The conventional dosage form of Ketoconazole (KZ) shows poor absorption due to rapid gastric emptying. Chitosan based mucoadhesive nanoparticles (NPs) of KZ were developed to efficiently release drug at its absorption window i.e. stomach and the site of action i.e. esophagus.

Method: The NPs were prepared by ionic gelation method. Concentration of polymer, cross-linking agent and ratio of drug/polymer as well as polymer/cross linking agent were optimized.

Results: NPs had 69.16?±?5.91% mucin binding efficiency, particle size of 382.6?±?2.384?nm, ζ potential of +48.1?mv and entrapment efficiency of 59.84 ± 1.088%. DSC thermogram indicated absence of any drug polymer interaction. The drug release was by controlled, non-fickian diffusion mechanism. Ex vivo diffusion studies were performed by emptying the stomach contents after 2?h to simulate in vivo gastric emptying. The results showed that drug diffusion from the solution across stomach mucosa stopped after emptying whereas that from the NPs continued upto 5?h. Hence we could conclude that the NPs must have adhered to the stomach mucosa and thereby would have been retained at this absorption site even after gastric emptying.

Conclusion: The orally delivered KZ loaded mucoadhesive NPs can be used as an efficient carrier for delivering drug at its absorption window i.e. the stomach and the site of action i.e. esophagus even after gastric emptying.     

Intradermal and follicular delivery of adapalene liposomes

Abstract

Background: Adapalene is a widely used topical anti-acne drug; however, it has many side effects. Liposomal drug delivery can play a major role by targeting delivery to pilosebaceous units, reducing side effects and offering better patient compliance.

Objective: To prepare and evaluate adapalene-encapsulated liposomes for their physiochemical and skin permeation properties.

Methods: A liposomal formulation of adapalene was prepared by the film hydration method and characterized for shape, size, polydispersity index (PDI), encapsulation efficiency and thermal behavior by techniques such as Zetasizer®, differential scanning calorimetry and transmission electron microscopy. Stability of the liposomes was evaluated for three months at different storage conditions. In vitro skin permeation studies and confocal laser microscopy were performed to evaluate adapalene permeation in pig ear skin and hair follicles.

Results: The optimized process and formulation parameters resulted in homogeneous population of liposomes with a diameter of 86.66?±?3.5?nm in diameter and encapsulation efficiency of 97.01?±?1.84% w/w. In vitro permeation studies indicated liposomal formulation delivered more drug (6.72?±?0.83?μg/cm²) in hair follicles than gel (3.33?±?0.26?μg/cm²) and drug solution (1.62?±?0.054?μg/cm²). Drug concentration delivered to the skin layers was also enhanced compared to other two formulations. Confocal microscopy images confirmed drug penetration in the hair follicles when delivered using the liposomal formulation.

Conclusion: Adapalene was efficiently encapsulated in liposomes and led to enhanced delivery in hair follicles, the desired target site for acne.     

Sustained-Release Dosage Form of Nicardipine Hydrochloride: Application of Factorial Design and Effect of Surfactant on Release Kinetics

Abstract

Microcapsules of nicardipine hydrochloride with core:wall ratios of 1:1, 2:1, and 1:2 were prepared by the coacervation-phase separation method, using ethyl-cellulose as the coating material. Two batches of nicardipine hydrochloride microscapsules were divided into size fraction by using standard sieves ranging from 840 μm to 476 pn. Dissolution rate studies from microcapsules were performed using the USP XXII basket method. The kinetic model according to the Rosin-Rammler-Sperling-Bennet-Weibull (RRSBW) distribution was applied for the parametric representation of the dissolution curves. Preparation and dissolution rate studies on the nicardipine hydrochloride microcapsules were pellformed and the influence of particle size, core:wall ratio, and the amount of nicardipine hydrochloride on the release rate was examined by 2³ factorial design. The sign@cance of the observed effects was tested with the F test. A surface active substance was added in the dissolution medium to understand how this substance effects the release of drug from ideal microcapsule form which is found by the findings of the 2³ factorial design. Dissolution studies were repeated with this ideal formulation using different ratio of Tween 20.

The results of this study suggested that the solubility and bioavailability of the sustained-release dosage forms of nicardipine hydrochloride using sullface active substances could be increased.     

A Study of the Effects of Sucrose Concentration,Lacquer Concentration and Coating Time on the Formulation of Stable and Effective Carbenicillin Indanyl Sodium Microcapsules

Abstract

Carbenicillin indanyl sodium, commonly known as Geocillin (GC), is an orally effective derivative of carbenicillin employed in the treatment of gram negative infections of the urinary tract. GC exhibits an extremely bitter taste which affects patient compliance upon oral dosing (1). A novel coating approach allows Geocillin to be prepared as a suspension for oral administration. GC is available only as a tablet.

Eudragit E100^R [EE] is a tasteless, acid soluble cationic polymer. Encapsulation of GC with [EE] inhibited its release in the mouth, thus overcoming its bitter taste. Dissolution studies were carried out in simulated gastric fluid and simulated intestinal fluid. Three factors, viz. sucrose concentration, lacquer concentration and coating time were evaluated to arrive at an optimally acceptable formulation.

The formulation containing GC and sucrose in the ratio of 1:3, suspension coated using a 5% w/w lacquer solution for 40 mins. yielded taste free microcapsules with optimal release characteristics.     

Improved oral bioavailability of valsartan using proliposomes: design,characterization and in vivo pharmacokinetics

Abstract

The objective of our investigational work was to develop a proliposomal formulation to improve the oral bioavailability of valsartan. Proliposomes were formulated by thin film hydration technique using different ratios of phospholipids:drug:cholesterol. The prepared proliposomes were evaluated for vesicle size, encapsulation efficiency, morphological properties, in vitro drug release, in vitro permeability and in vivo pharmacokinetics. In vitro drug-release studies were performed in simulated gastric fluid (pH 1.2) and purified water using dialysis bag method. In vitro drug permeation was studied using parallel artificial membrane permeation assay (PAMPA), Caco-2 monolayer and everted rat intestinal perfusion techniques. In vivo pharmacokinetic studies were conducted in male Sprague Dawley (SD) rats. Among the proliposomal formulations, F-V was found to have the highest encapsulation efficiency of 95.6?±?2.9% with a vesicle size of 364.1?±?14.9?nm. The in vitro dissolution studies indicated an improved drug release from proliposomal formulation, F-V in comparison to pure drug suspension in both, purified water and pH 1.2 dissolution media after 12?h. Permeability across PAMPA, Caco-2 cell and everted rat intestinal perfusion studies were higher with F-V formulation as compared to pure drug. Following single oral administration of F-V formulation, a relative bioavailability of 202.36% was achieved as compared to pure valsartan.     

Development of modified in situ gelling oral liquid sustained release formulation of dextromethorphan

Context: Alternative strategies are being employed to develop liquid oral sustained release formulation. These included ion exchange resin, sustained release suspensions and in situ gelling systems. The later mainly utilizes alginate solutions that form gels upon contact with calcium which may be administered separately or included in the alginate solution as citrate complex. This complex liberates calcium in the stomach with subsequent gellation. The formed gel can break after gastric emptying leading to dose dumping.

Objective: Development of modified in situ gelling system which sustain dextromethorphan release in the stomach and intestine.

Methods: Solutions containing alginate with calcium chloride and sodium citrate were initially prepared to select the formulation sustaining the release in the stomach. The best formulation was combined with chitosan. All formulations were characterized with respect to flow, gelling capacity, gelling strength and drug release.

Results: Increasing the concentration of alginate increased the gelling capacity and strength and reduced the rate of drug release in gastric conditions with 2% w/v alginate being the best formulation. However, these formulations failed to sustain the release in the intestinal conditions. Incorporation of chitosan with alginate increased the gelling capacity and strength and reduced the rate of drug release compared to alginate only system. The effect was optimum in formulation containing 1.5% w/v chitosan. The sustained release pattern was maintained both in the gastric and intestinal conditions and was comparable to that obtained from the marketed product.

Conclusion: Alginate-chitosan based in situ gelling system is promising for developing liquid oral sustained release.     

Compression of Microcapsules I: Effect of Excipients and Pressure on Drug Release

Abstract

Microcapsules containing phenylpropanolamine-resin complexes were compressed with various diluents. Compression of microcapsules produced an increase in the release rate. An average reduction of 0.50 hours was observed when Emdex or Fast Flo Lactose were compared to Avicel at various pressures (35 to 281 MPa). Increasing the amount of microcapsules in the formulation reduced the T50% with all three diluents     

Release of Theophylline from Ethyl Cellulose Mecrocapsues Alone and in Conjuction with Fat Embedded (Precirol®) Granules and Hydroxypropyl Methycellulose

Abstract

Microcapsules of theophylline with ethyl cellulose were prepared by coacervation technique using cabosil® (silicon dioxide) as separant. Tablets were prepared from microcapsules, microcapsules + theophylline fat embedded granules, and microcapsules and hydroxypropyl methylcellulose 4000 (HPMC). Release was studied in vitro by the rotating basket method. Prolonged release of theophylline was observed from microcapsules with no drug dumping. The release from microcapsules was of first-order whereas that from all the tablet formulation was diffusion controlled according to the Higuchi model. Good correlation was found between release rate and core:wall ratio for all the systems. Decrease in hardness of tablets made from microcapsules alone decreased the release rate, indicating damage of microcapsules during compression. The tablets compressed from fat embedded granules, microcapsules with fat embedded granules, and microcapsules with HPMC gave a desired release for a 74 hour sustained release preparation.     

Design and characterization of enteric-coated controlled release mucoadhesive microcapsules of Rabeprazole sodium

The objectives of present work was to design and characterize the rabeprazole sodium loaded microcapsules prepared by solvent evaporation technique using ethyl cellulose (EC) based various mucoadhesive polymer, followed by a triple coating with Eudragit L100. The Box-behnken design (BBD) was applied for optimization of formulations containing EC, HPMCK100M and Eudragit L100 as factors for selected responses like entrapment efficiency, mucoadhesive property and drug release in 24 h. The prepared microcapsules were characterized for particle size, drug content, swelling index, mucoadhesive strength, and in vivo antiulcer activity. FT-IR studies revealed that there was no drug-polymer interaction. SEM studies revealed that microcapsules were non-aggregated, spherical shape and smooth appearance. In vitro drug release data from microcapsules was fitted to different kinetic models to explain release profiles. The correlation coefficient value (r²) indicated that the drug release followed Higuchi model. Analysis of variance (ANOVA) showed significant difference in the release of drug from all formulations at p < 0.05 level. Accelerated stability study of optimized formulation (F4) upto 6 months showed there was no change in drug content and release characteristics during storage. In vivo antiulcer activity showed that the optimized microcapsules were able to protect rat stomach against ulcer formation vis-à-vis aqueous solution of the drug showed only negligible and minimum effect.     

Nanoethosomal formulation of gammaoryzanol for skin-aging protection and wrinkle improvement: a histopathological study

Background: Free radical scavengers and antioxidants, with the main focus on enhanced targeting to the skin layers, can provide protection against skin ageing.

Objective: The aim of the present study was to prepare nanoethosomal formulation of gammaoryzanol (GO), a water insoluble antioxidant, for its dermal delivery to prevent skin aging.

Methods: Nanoethosomal formulation was prepared by a modified ethanol injection method and characterized by using laser light scattering, scanning electronic microscope (SEM) and X-ray diffraction (XRD) techniques. The effects of formulation parameters on nanoparticle size, encapsulation efficiency percent (EE%) and loading capacity percent (LC%) were investigated. Antioxidant activity of GO-loaded formulation was investigated in vitro using normal African green monkey kidney fibroblast cells (Vero). The effect of control and GO-loaded nanoethosomal formulation on superoxide dismutase (SOD) and malondialdehyde (MDA) content of rat skin was also probed. Furthermore, the effect of GO-loaded nanoethosomes on skin wrinkle improvement was studied by dermoscopic and histological examination on healthy humans and UV-irradiated rats, respectively.

Results: The optimized nanoethosomal formulation showed promising characteristics including narrow size distribution 0.17?±?0.02, mean diameter of 98.9?±?0.05?nm, EE% of 97.12?±?3.62%, LC% of 13.87?±?1.36% and zeta potential value of –15.1?±?0.9?mV. The XRD results confirmed uniform drug dispersion in the nanoethosomes structure. In vitro and in vivo antioxidant studies confirmed the superior antioxidant effect of GO-loaded nanoethosomal formulation compared with control groups (blank nanoethosomes and GO suspension).

Conclusions: Nanoethosomes was a promising carrier for dermal delivery of GO and consequently had superior anti-aging effect.     

Application of Flow-Through Dissolution Method for the Evaluation of Oral Formulations of Nifedipine

Abstract

The drug release characteristics of three oral formulations (one conventional and 2 extended-release) of nifedipine were evaluated using a flow-through apparatus. The experiments were conducted for 4 to 24 hours using water or phosphate buffer (0.05 or 0.1 M; pH 7.4) with or without solubilizing agent, Tween, as a dissolution medium at a flow rate of 12.5 mL/min. The drug concentrations were determined using an HPLC method based on ratios of peak heights corresponding to UV absorbances at 254 nm for nifedipine and nitrendipine (internal standard). Dissolution characteristics in various media correspond to the nifedipine solubility in the medium. Peak nifedipine concentrations with 0.05 M phosphate buffer containing 0.5% Tween were significantly higher than those in the medium without Tween (21.5±1.0 vs 8.3±0.2 μg/mL, p c 0.001). Using a 0.05 M phosphate buffer with no Tween, the products tested showed distinct dissolution profiles representative of the respective formulation type. The conventional release product (10 mg) showed a higher mean peak nifedipine concentration (C_max,d) of 49.5±2.4 pg/mL (p < 0.001) attained at (t_max,d) 0.46±0.05 h as compared to those of modified-release products. The corresponding mean values for the modified-release tablets were 8.3±0.2 and 2.6±.3 μg/mL for C_max,d, and 0.28±0.03 and 12.0±3.8 h for t_max,d for the 20 and 30 mg tablets, respectively. Area under the concentration-time curves (AUC_o-t,d) for the 10, 20 and 30 mg formulations were 12.3±0.4,20.5±2.6 and 32.6±3.7 μg.h/mL, respectively (p < 0.001). As the dissolution profiles are similar to those of plasmakerum drug concentrations-time profiles obtained from clinical studies, application of this dissolution method, along with the derived in vitro drug-release kinetics parameters for potential correlation with in vivo parameters are discussed. The results of this study show that, compared to the USP dissolution method using apparatus 1 or 2, the flow-through dissolution system offers a potentially better alternative to assess drug release characteristics for different types of formulations, especially for drugs of low aqueous solubility such as nifedipine.     

Taste masking of azithromycin by resin complex and sustained release through interpenetrating polymer network with functionalized biopolymers

Abstract

Objective: The objective was to evaluate taste masking of azithromycin (AZI) by ion exchange resins (IERs) and the formation of covalent semi interpenetrating polymer network (IPN) beads using chitosan (CS) and sodium carboxylated agarose (SCAG) for sustained release of drug.

Methods: Methacrylic acid (MAA)-based IERs were prepared by suspension polymerization method. Drug release complexes (DRCs) were prepared by different drug:resin ratios i.e. 1:1, 1:2 and 1:4. The resultant DRCs were characterized using DSC, FTIR, PXRD, in vivo and in vitro taste masking, and in vitro drug release at gastric pH. IPN beads were prepared by entrapping DRCs with bio polymers and cross linked with trisodium citrate (NaCIT), and further cross-linked with glutaraldehyde (GA) for sustained release of AZI.

Results: In vitro and in vivo taste masking studies showed that MD1:4 DRC formulation was optimal. The release of AZI from DRC was found to be very fast at gastric pH i.e. 97.37?±?1.02% within 45?min. The formation of IPN beads was confirmed by FTIR. The release of drug from IPN beads at gastric and intestinal pH was found to be “<28% and <60%”, respectively. The release kinetics showed Fickian diffusion profile for ionically cross-linked beads and zero-order release mechanism for GA cross-linking beads.

Conclusions: DRCs can be effectively used for taste masking and newly formulated IPN beads demonstrated sustained release of AZI.     

Study of controlled-release floating tablets of dipyridamole using the dry-coated method

Dipyridamole (DIP), having a short biological half-life, has a narrow absorption window and is primarily absorbed in the stomach. So, the purpose of this study was to prepare controlled-release floating (CRF) tablets of dipyridamole by the dry-coated method. The influence of agents with different viscosity, hydroxypropylmethylcellulose (HPMC) and polyvinylpyrollidon K30 (PVP K30) in the core tablet and low-viscosity HPMC and PVP K30 in the coating layer on drug release, were investigated. Then, a study with a three-factor, three-level orthogonal experimental design was used to optimize the formulation of the CRF tablets. After data processing, the optimized formulation was found to be: 80?mg HPMC K4M in the core tablet, 80?mg HPMC E15 in core tablet and 40?mg PVP K30 in the coating layer. Moreover, an in vitro buoyancy study showed that the optimized formulation had an excellent floating ability and could immediately float without a lag time and this lasted more than 12?h. Furthermore, an in vivo gamma scintigraphic study showed that the gastric residence time of the CRF tablet was about 8?h.     

Enhancement of oral bioavailability of anti-HIV drug rilpivirine HCl through nanosponge formulation*

Objective: To synthesize β cyclodextrin nanosponges using a novel and efficient microwave mediated method for enhancing bioavailability of Rilpivirine HCl (RLP).

Significance: Belonging to BCS class II RLP has pH dependent solubility and poor oral bioavailability. However, a fatty meal enhances its absorption hence the therapy indicates that the dosage form be consumed with a meal. But then it becomes tedious and inconvenient to continue the therapy for years with having to face the associated gastric side effects such as nausea.

Method: Microwave synthesizer was used to mediate the poly-condensation reaction between β-cyclodextrin and cross-linker diphenylcarbonate. Critical parameters selected were polymer to cross-linker ratio, Watt power, reaction time and solvent volume. Characterization studies were performed using FTIR, DSC, SEM, ¹H-NMR and PXRD. Molecular modeling was applied to confirm the possibility of drug entrapment. In vitro drug dissolution followed by oral bioavailability studies was performed in Sprawley rats. Samples were analyzed using HPLC.

Results: Microwave synthesis yields para-crystalline, porous nanosponges (～205?nm). Drug entrapment led to enhancement of solubility and a two-fold increase in drug dissolution (P?C_max and AUC_0-∞ increases significantly (C_max of NS～ 586?±?5.91?ng/mL; plain RLP ～310?±?5. 74?ng/mL).

Conclusion: The approach offers a comfortable dosing zone for AIDs patients, negating the requirement of consuming the formulation in a fed state due to enhancement in drugs’ oral bioavailability.     

A quality-by-design study to develop Nifedipine nanosuspension: examining the relative impact of formulation variables,wet media milling process parameters and excipient variability on drug product quality attributes

Abstract

Wet milling is a multifunctional and the most common method to prepare a drug nanosuspension for improving the bioavailability of poorly water soluble drugs. A suitable way of preparing a high drug-loaded nifedipine nanosuspension using wet stirred media milling was investigated in the present study. Nifedipine, a poorly water soluble drug, was selected as a model drug to enhance its dissolution rate and oral bioavailability by preparing an appropriate crystalline nanosuspension. Process parameters, such as milling media volume, milling speed and milling time, were optimized using the one variable at a time (OVAT) approach. A similar method was used to select an appropriate polymeric stabilizer and a surfactant from different categories of polymeric stabilizers (HPC SL, HPC SSL Soluplus®, Kollidon^® VA 64 and HPMC E 15) and surfactants (Poloxamer 407, Kolliphor TPGS and Docusate sodium). A systematic optimization of critical formulation parameters (such as drug concentration, polymer concentration and surfactant concentration) was performed with the aid of the Box-Behnken design. Mean particle size, polydispersity index and zeta potential as critical quality attributes (CQAs) were selected in the design for the evaluation and optimization of the formulation and validation of the improved product. The nifedipine nanosuspension that was prepared using HPC and poloxamer 407 was found to be most stable with the lowest mean particle size as compared with the formulations prepared using other polymeric stabilizers and surfactants. The optimized formulation was further spray-dried and characterized using the Fourier Transform Infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), polarized light microscopy (PLM) and in-vitro dissolution study. Results have shown no interaction between the drug particles and stabilizers, nor a reduction in the crystallinity of drug, nor an increase in the saturation solubility and rapid in vitro dissolution as compared with pure nifedipine crystals. Thus, the current study supports the suitability of the wet stirred media milling method and a combination of HPC SSL and poloxamer 407 as stabilizers for the preparation of nifedipine nanosuspension.     

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.     

Thermal sintering: a novel technique used in the design,optimization and biopharmaceutical evaluation of propranolol HCl gastric floating tablets

The objective of the present investigation was to study the applicability of thermal sintering technique for the development of gastric floating tablets of propranolol HCl. Formulations were prepared using four independent variables, namely (i) polymer quantity, (ii) sodium bicarbonate concentration, (iii) sintering temperature and (iv) sintering time. Floating lag time and t₉₅ were taken as dependent variables. Tablets were prepared by the direct compression method and were evaluated for physicochemical properties, in vitro buoyancy and dissolution studies. From the drug release studies, it was observed that drug retarding property mainly depends upon the sintering temperature and time of exposure. The statistically optimized formulation (PTSso) was characterized by Fourier transform infrared spectroscopy and differential scanning calorimetry studies, and no significant chemical interaction between drug and polymer was observed. Optimized formulation was stable at accelerated conditions for a period of six months. PTSso was evaluated for in vivo buoyancy studies in humans for both fed and fasted states and found that gastric residence time of the floating tablets were enhanced by fed stage but not in fasted state. Optimized formulation PTSso and commercial formulation Ciplar LA 80 were subjected to bioavailability studies in healthy human volunteers by estimating pharmacokinetic parameters such as C_max, T_max, area under curve (AUC), elimination rate constant (K_el), biological half-life (t_1/2) and mean residence time (MRT). There was a significant increase in the bioavailability of the propranolol HCl from PTSso formulation, which was evident from increased AUC levels and larger MRT values than Ciplar LA 80.     

Development of Extended Release Dosage Forms Using Non-Uniform Drug Distribution Techniques

ABSTRACT

Development of an extended release oral dosage form for nifedipine using the non-uniform drug distribution matrix method was conducted. The process conducted in a fluid bed processing unit was optimized by controlling the concentration gradient of nifedipine in the coating solution and the spray rate applied to the non-pareil beads. The concentration of nifedipine in the coating was controlled by instantaneous dilutions of coating solution with polymer dispersion transported from another reservoir into the coating solution at a controlled rate. The USP dissolution method equipped with paddles at 100 rpm in 0.1 N hydrochloric acid solution maintained at 37°C was used for the evaluation of release rate characteristics. Results indicated that (1) an increase in the ethyl cellulose content in the coated beads decreased the nifedipine release rate, (2) incorporation of water-soluble sucrose into the formulation increased the release rate of nifedipine, and (3) adjustment of the spray coating solution and the transport rate of polymer dispersion could achieve a dosage form with a zero-order release rate. Since zero-order release rate and constant plasma concentration were achieved in this study using the non-uniform drug distribution technique, further studies to determine in vivo/in vitro correlation with various non-uniform drug distribution dosage forms will be conducted.     

Development of a topical mupirocin spray for antibacterial and wound-healing applications

Objective: The aim of this study was to develop mupirocin topical spray using Eudragit E100 as a film-forming agent for the treatment of bacterial skin infections as well as to promote wound healing.

Materials and methods: Twenty-seven of mupirocin formulations were formulated containing Eudragit E100 and other excipients. Mupirocin spray was prepared by aerosol crimping and filling machine using HFA-134a as a propellant. The formulations were evaluated for their stability and physicochemical properties. The factorial study was applied to evaluate the effects of glycerol and PEG400 on mupirocin-loaded Eudragit E100 films. The optimized formulation was assessed of drug release, antibacterial activities and in vitro cell line studies in comparison to the ointment formulation.

Results and discussion: Mupirocin sprays were formulated and optimized to obtain the formulation with excellent physicochemical and mechanical properties of the dressing film. The formulation had an excellent stability up to a year with more than 80% of mupirocin content. Mupirocin was released from the film up to 90% within 2?h. The formulation had a potent antibacterial effect against S. aureus and S. epidermidis. The formulation was safe to use as a topical formulation that had no toxicity to keratinocytes, fibroblasts and monocytes. The formulation also had an antiendotoxin effect without stimulating the production of NO and inflammatory cytokines (IL-1β and TNF-α).

Conclusions: Mupirocin topical spray was successful developed as a topical formulation and can be used instead of the ointment formulation. Animal experiments are warranted to further emphasize the safe use in the human skin.