Effect of Device Design on the Aerosolization of a Carrier-Based Dry Powder Inhaler—a Case Study on Aerolizer® Foradile®

The objective of this study is to investigate the effect of device design of the Aerolizer^® on the aerosolization of a carrier-based dry powder inhaler formulation (Foradile^®). The Aerolizer was modified by reducing the air inlet size and mouthpiece length to 1/3 of the original dimensions, or by increasing the grid voidage. Aerosolization of the powder formulation was assessed on a multi-stage liquid impinger at air flow rates of 30, 60, and 100 L/min. Coupled CFD-DEM simulations were performed to investigate the air flow pattern and particle impaction. There was no significant difference in the aerosolization behavior between the original and 1/3 mouthpiece length devices. Significant increases in FPF total and FPF emitted were demonstrated when the inlet size was reduced, and the results were explained by the increases in air velocity and turbulence from the CFD analysis. No significant differences were shown in FPF total and FPF emitted when the grid voidage was increased, but more drugs were found to deposit in induction port and to a lesser extent, the mouthpiece. This was supported by the CFD-DEM analysis which showed the particle–device collisions mainly occurred in the inhaler chamber, and the cross-grid design increased the particle–device collisions on both mouthpiece and induction port. The air inlet size and grid structure of the Aerolizer^® were found to impact significantly on the aerosolization of the carrier-based powder.     

The Cohesive-Adhesive Balances in Dry Powder Inhaler Formulations II: Influence on Fine Particle Delivery Characteristics

PURPOSE: To investigate the influence of the cohesive-adhesive balances on dry powder formulation aerosolization and delivery characteristics. METHODS: De-agglomeration properties of pharmaceutical powders were investigated using an Aerosizer at various shear forces. Aerosol drug deposition properties of drug-only formulations and carrier-based formulations were investigated using a low-resistance device (Rotahaler) and a high-resistance device (Turbuhaler) via a twin-stage impinger. RESULTS: A paradoxical relationship between particle cohesive strength and de-agglomeration efficiencies of drug-only formulations was observed, where an increase in cohesive strength led to a higher fine particle fraction. A possible explanation for the variation in the fluidization and aerosolization properties between low and high cohesive particles was modeled on the relationship between cohesion, metastable agglomerate size, and the resulting aerodynamic drag force acting on the fluidized agglomerates. The addition of a fine particle lactose carrier influenced the drug deposition patterns in different ways depending on the relative cohesive and adhesive force balances within the formulation. CONCLUSIONS: The use of the colloid Atomic Force Microscrope (AFM) technique in combination with the cohesive-adhesive balance (CAB) system provides a novel preformulation tool for investigating the likely behavior of a dry powder formulation and a possible means of interpreting the possible de-aggregation and dispersion mechanisms of carrier-based formulations.     

In vitro characterization of nebulizer delivery of liposomal amphotericin B aerosols

Pharmaceutical aerosols have the potential to prevent pulmonary infectious diseases. Liposomal amphotericin B (LAMB, Ambisome^?, Astellas Pharma US, Deerfield, IL, USA) is approved as an intravenous infusion for empiric treatment of presumed fungal infections in neutropenic, febrile patients, as well as patients infected with Aspergillus, Cryptococcus, and other fungal pathogens. In this study, four different nebulizers were tested for their ability to deliver LAMB in aerodynamic droplet-size ranges relevant to lung deposition by an inertial sampling technique Mass median aerodynamic diameter (MMAD) and fine particle fraction percent <3.3 μm (FPF_3.3) and <5.8 μm (FPF_5.8) were determined by cascade impaction during a 2?min sampling period for each of three trials of all nebulizers. The MMADs for all nebulizers ranged from 1.72?±?0.11 μm to 2.89?±?0.12 μm; FPF_3.3 and FPF_5.8 were approximately 80% and 90%, respectively. Although all nebulizers appear acceptable for delivery of LAMB, the Pari LC Star and the Aeroeclipse II were considered the best in terms of delivery of aerosol efficiently and the proportion suitable for lung deposition. Additional research on pulmonary delivery and clinical tolerability is warranted.     

Aerosol Dispersion of Respirable Particles in Narrow Size Distributions Using Drug-Alone and Lactose-Blend Formulations

PURPOSE: To examine the effect of formulation type on the aerosolization of respirable particles in narrow size distributions. METHODS: Aerosol dispersion of two formulation types (drug alone and 2% w/w drug-lactose blends) containing micronized or spray-dried fluticasone propionate (FP) particles (d50% = 1.3 to 9.6 microm, GSD = 1.8 to 2.2) were examined using cascade impaction at 60 l/min with low and high resistance inhaler devices: Rotahaler and Inhalator, respectively. RESULTS: The aerosol dispersion of FP particles was significantly affected by the particle size, particle type, inhaler device, and formulation type. Interactions were observed between all factors. Generally, greater powder entrainment was obtained with smaller d50%. Higher emitted doses were obtained from drug-alone formulations of spray-dried FP particles and lactose blends of micronized FP particles. Greater aerosol dispersion of spray-dried FP particles was obtained using lactose-blend formulations with d50% around 4 microm. Greater aerosol dispersion of micronized FP particles was obtained using formulations of drug alone. Larger d50% produced larger mass median aerodynamic diameters. CONCLUSIONS: Small changes in the particle size within the 1-10-microm range exerted a major influence on aerosol dispersion of jet-milled and spray-dried FP particles using drug-alone and lactose-blend formulations.     

Effects of formulation and operating variables on Zanamivir dry powder inhalation characteristics and aerosolization performance

Abstract

The objective of this study was to investigate the influence of formulation and operating variables on the physical characteristics and aerosolization performance of zanamivir spary-dried powders for inhalation. Spray-dried samples of zanamivir, zanamivir/mannitol and zanamivir/mannitol/leucine were prepared from their corresponding aqueous solutions under the same conditions to study the influence of the composition, and zanamivir/mannitol/leucine (1/1/3 by weight) formulation was used for investigation of the effect of the preparation process. Dry powders were characterized afterwards for different physical properties, including morphology, particle size, flowability, density and moisture absorption. The in vitro deposition was also evaluated after the aerosolization of powders at 100?L?min^?1 via the Aerolizer® into a Next Generation Impactor (NGI). The highest FPF of 41.40?±?1.1% was obtained with a zanamivir/mannitol/leucine ratio of 1/1/3, which had an average D_g of 3.11?±?0.13?μm and an angle of repose of 36°^?±?1. It was found that the influence of the preparation process on zanamivir spary-dried powders characteristics and aerosolization properties was relatively small, but the influence of the composition was relatively large. Optimization of DPI can be achieved by selecting the most appropriate formulation and preparation process.     

The Role of Capsule on the Performance of a Dry Powder Inhaler Using Computational and Experimental Analyses

Purpose To study the fundamental effects of the spinning capsule on the overall performance of a dry powder inhaler (Aerolizer®).Methods The capsule motion was visualized using high-speed photography. Computational fluid dynamics (CFD) analysis was performed to determine the flowfield generated in the device with and without the presence of different sized capsules at 60 l min^–1. The inhaler dispersion performance was measured with mannitol powder using a multistage liquid impinger at the same flowrate.Results The capsule size (3, 4, and 5) was found to make no significant difference to the device flowfield, the particle-device impaction frequency, or the dispersion performance of the inhaler. Reducing the capsule size reduced only the capsule retention by 4%. In contrast, without the presence of the spinning capsule, turbulence levels were increased by 65%, FPF_Em (wt% particles 6.8 m in the aerosol referenced against the amount of powder emitted from the device) increased from 59% to 65%, while particle-mouthpiece impaction decreased by 2.5 times. When the powder was dispersed from within compared to from outside the spinning capsule containing four 0.6 mm holes at each end, the FPF_Em was increased significantly from 59% to 76%, and the throat retention was dropped from 14% to 6%.Conclusions The presence, but not the size, of a capsule has significant effects on the inhaler performance. The results suggested that impaction between the particles and the spinning capsule does not play a major role in powder dispersion. However, the capsule can provide additional strong mechanisms of deagglomeration dependent on the size of the capsule hole.     

Development of a High Efficiency Dry Powder Inhaler: Effects of Capsule Chamber Design and Inhaler Surface Modifications

Purpose

The objective of this study was to explore the performance of a high efficiency dry powder inhaler (DPI) intended for excipient enhanced growth (EEG) aerosol delivery based on changes to the capsule orientation and surface modifications of the capsule and device.

Methods

DPIs were constructed by combining newly designed capsule chambers (CC) with a previously developed three-dimensional (3D) rod array for particle deagglomeration and a previously optimized EEG formulation. The new CCs oriented the capsule perpendicular to the incoming airflow and were analyzed for different air inlets at a constant pressure drop across the device. Modifications to the inhaler and capsule surfaces included use of metal dispersion rods and surface coatings. Aerosolization performance of the new DPIs was evaluated and compared with commercial devices.

Results

The proposed capsule orientation and motion pattern increased capsule vibrational frequency and reduced the aerosol MMAD compared with commercial/modified DPIs. The use of metal rods in the 3D array further improved inhaler performance. Coating the inhaler and capsule with PTFE significantly increased emitted dose (ED) from the optimized DPI.

Conclusions

High efficiency performance is achieved for EEG delivery with the optimized DPI device and formulation combination producing an aerosol with MMAD?<?1.5 μm, FPF_<5μm/ED?>?90%, and ED?>?80%.     

The Role of Fines in the Modification of the Fluidization and Dispersion Mechanism Within Dry Powder Inhaler Formulations

PURPOSE: To investigate the role of in situ generated fine excipient particles on the fluidization and aerosolization properties of dry powder inhaler (DPI) formulations. MATERIALS AND METHODS: Carrier based DPI formulations were prepared under low and high shear blending. Powder rheometery was utilized to measure bulk powder properties in a consolidated and aerated state. Powder fluidization and aerosolization characteristics were related to bulk powder properties using high speed imaging and inertial impaction measurements. RESULTS: High shear blending of formulations resulted in the in situ generation of excipient fines, which corresponded to an increase in aerosolization efficiency. The generation of fines were shown to increase the tensile strength and free volume of the carrier, which resulted in a characteristic change in the fluidization properties, as observed by high speed imaging. The increase in minimum fluidization velocity and aerodynamic drag forces required to aerate the powder may provide the source of energy for the increase in fine particle re-suspension. CONCLUSIONS: The in situ generation of excipient fines affect bulk powder properties of DPI formulations, which directly affects fluidization and aerosolization behaviour of DPI formulations. The study suggests an alternative mode of action by which fines increase DPI formulation performance.     

Development and Comparison of New High-Efficiency Dry Powder Inhalers for Carrier-Free Formulations

High-efficiency dry powder inhalers (DPIs) were developed and tested for use with carrier-free formulations across a range of different inhalation flow rates. Performance of a previously reported DPI was compared with two new designs in terms of emitted dose (ED) and aerosolization characteristics using in vitro experiments. The two new designs oriented the capsule chamber (CC) at different angles to the main flow passage, which contained a three-dimensional (3D) rod array for aerosol deaggregation. Computational fluid dynamics simulations of a previously developed deaggregation parameter, the nondimensional specific dissipation (NDSD), were used to explain device performance. Orienting the CC at 90° to the mouthpiece, the CC₉₀-3D inhaler provided the best performance with an ED = 73.4%, fine particle fractions (FPFs) less than 5 and 1 μm of 95.1% and 31.4%, respectively, and a mass median aerodynamic diameter (MMAD) = 1.5 μm. For the carrier-free formulation, deaggregation was primarily influenced by capsule aperture position and the NDSD parameter. The new CC-3D inhalers reduced the percent difference in FPF and MMAD between low and high flows by 1–2 orders of magnitude compared with current commercial devices. In conclusion, the new CC-3D inhalers produced extremely high-quality aerosols with little sensitivity to flow rate and are expected to deliver approximately 95% of the ED to the lungs.     

Corrugated surface microparticles with chitosan and levofloxacin for improved aerodynamic performance

Corrugated surface microparticles comprising levofloxacin (LEV), chitosan and organic acid were prepared using the 3-combo spray drying method. The amount and the boiling point of the organic acid affected the degree of roughness. In this study, we tried to improve the aerodynamic performance and increase aerosolization by corrugated surface microparticle for lung drug delivery efficiency as dry powder inhaler. HMP175 L20 prepared with 175 mmol propionic acid solution was corrugated more than HMF175 L20 prepared with 175 mmol formic acid solution. The ACI and PIV results showed a significant increase in aerodynamic performance of corrugated microparticles. The FPF value of HMP175 L20 was 41.3% ± 3.9% compared with 25.6% ± 7.7% of HMF175 L20. Corrugated microparticles also showed better aerosolization, decreased x-axial velocity, and variable angle. Rapid dissolution of drug formulations was observed in vivo. Low doses administered to the lungs achieved higher LEV concentrations in the lung fluid than high doses administered orally. Surface modification in the polymer-based formulation was achieved by controlling the evaporation rate and improving the inhalation efficiency of DPIs.     

Drug-lactose binding aspects in adhesive mixtures: controlling performance in dry powder inhaler formulations by altering lactose carrier surfaces

For dry powder inhaler formulations, micronized drug powders are commonly mixed with coarse lactose carriers to facilitate powder handling during the manufacturing and powder aerosol delivery during patient use. The performance of such dry powder inhaler formulations strongly depends on the balance of cohesive and adhesive forces experienced by the drug particles under stresses induced in the flow environment during aerosolization. Surface modification with appropriate additives has been proposed as a practical and efficient way to alter the inter-particulate forces, thus potentially controlling the formulation performance, and this strategy has been employed in a number of different ways with varying degrees of success. This paper reviews the main strategies and methodologies published on surface coating of lactose carriers, and considers their effectiveness and impact on the performance of dry powder inhaler formulations.     

Production of Inhalation Phage Powders Using Spray Freeze Drying and Spray Drying Techniques for Treatment of Respiratory Infections

Purpose

The potential of aerosol phage therapy for treating lung infections has been demonstrated in animal models and clinical studies. This work compared the performance of two dry powder formation techniques, spray freeze drying (SFD) and spray drying (SD), in producing inhalable phage powders.

Method

A Pseudomonas podoviridae phage, PEV2, was incorporated into multi-component formulation systems consisting of trehalose, mannitol and L-leucine (F1?=?60:20:20 and F2?=?40:40:20). The phage titer loss after the SFD and SD processes and in vitro aerosol performance of the produced powders were assessed.

Results

A significant titer loss (~2 log) was noted for droplet generation using an ultrasonic nozzle employed in the SFD method, but the conventional two-fluid nozzle used in the SD method was less destructive for the phage (~0.75 log loss). The phage were more vulnerable during the evaporative drying process (~0.75 log further loss) compared with the freeze drying step, which caused negligible phage loss. In vitro aerosol performance showed that the SFD powders (~80% phage recovery) provided better phage protection than the SD powders (~20% phage recovery) during the aerosolization process. Despite this, higher total lung doses were obtained for the SD formulations (SD-F1?=?13.1?±?1.7?×?10⁴ pfu and SD-F2?=?11.0?±?1.4?×?10⁴ pfu) than from their counterpart SFD formulations (SFD-F1?=?8.3?±?1.8?×?10⁴ pfu and SFD-F2?=?2.1?±?0.3?×?10⁴ pfu).

Conclusion

Overall, the SD method caused less phage reduction during the powder formation process and the resulted powders achieved better aerosol performance for PEV2.

     

The development of a novel high-dose pressurized aerosol dry-powder device (PADD) for the delivery of pumactant for inhalation therapy.

The performance of a novel dry powder inhaler designed to deliver exceptionally high doses was investigated using pumactant as a model powder. Pumactant (a synthetic lung surfactant consisting of a phospholipid mixture), with a 90th percentile particle size of 2.92 microm is highly cohesive, has a high moisture affinity (6.2% w/w at 45% RH), and is predominantly amorphous. The device (pressurized aerosol dry-powder delivery [PADD]) utilizes pressurized gas to aerosolize a powder bed from a reservoir and delivers it through a conventional mouthpiece. The influence of loaded dose on dry powder delivery and can pressure on aerosolization efficiency was investigated. Analysis of the delivered dose studies suggested a linear relationship between loaded dose and delivered dose (R(2) = 0.96, for loaded doses of 0-250 mg), with a delivery efficiency of 70%. Analysis of the aerosolization efficiency using a Marple Miller type impactor suggested fine particle fractions (particles with an aerodynamic diameter of <5 microm) of approximately 30% using canister pressures of 8-14 bars. These results indicate that the PADD device may be a useful tool in delivering high-dose medicaments, as a carrier-free formulation, to the deep lung.     

Towards a More Desirable Dry Powder Inhaler Formulation: Large Spray-Dried Mannitol Microspheres Outperform Small Microspheres

Purpose

To investigate, for the first time, the performance of a dry powder inhaler (DPI, Aerolizer^®) in the case of a model drug (i.e. albuterol sulphate) formulated with spray dried mannitol carrier particles with homogeneous shape and solid–state form but different sizes.

Methods

Spray dried mannitol (SDM) particles were characterized in terms of size, surface area, morphology, water content, solid–state, density and electrostatic charge by a novel approach. DPI formulations composed of SDM and albuterol sulphate (AS) were prepared and evaluated in terms of drug content homogeneity and in vitro aerosolization performance.

Results

All SDM particles generated similar fine particle fractions of AS. Formulations consisting of larger SDM particles demonstrated better drug content homogeneity, reduced amounts of drug loss and reduced oropharyngeal deposition. Comparing different SDM products demonstrated that SDM powders with relatively poorer flowability, wider size distributions and higher charge density generated DPI formulations with poorer drug content homogeneity and deposited higher amount of drug on the inhaler, mouthpiece adaptor and throat. DPI formulation total desirability increased linearly with the mean diameter of SDM.

Conclusion

Particle shape and solid–state form of mannitol could dominate over carrier size, bulk density, flowability and charge in terms of determining the aerosolization behaviour of AS formulated with mannitol carrier, at least within the experimental protocols applied in the present study.     

Effects of very low dose and enteric-coated acetylsalicylic acid on prostacyclin and thromboxane formation and on bleeding time in healthy subjects

Objective: Low dose acetylsalicylic acid (ASA) is widely used as an anti-aggregatory agent in the primary and secondary prevention of cardiovascular diseases. In an effort to spare prostacyclin formation and to reduce gastrointestinal side-effects, both very low doses and enteric-coated formulations of ASA have been introduced. However, it still remains unclear whether these different formulations and dosages are equally effective with respect to inhibition of platelet aggregation and thromboxane A₂ (TXA₂) formation. Methods: In a randomized study, we therefore investigated the effects of 100?mg ASA plain (p), 100?mg ASA enteric-coated (ec) and 40?mg ASA (p) to 36 healthy male subjects given for 7 days on platelet aggregation and endogenous prostanoid formation rates. Platelet aggregation and platelet TXB₂ release in platelet rich plasma (PRP) and serum TXB₂ and 6-keto-PGF_1α levels were determined at baseline and after 7 days of each medication. The urinary metabolites of TXA₂ (2,3-dinor-TXB₂) and prostacyclin (2,3-dinor-6-keto-PGF_1α) were measured by gas chromatography/tandem mass spectrometry in 24-h-urines at baseline and on day 7 of each medication. Results: Collagen-induced platelet aggregation was 73.1?±?1.6% of maximal aggregation at baseline. It was inhibited by 68.9%, 58.6% and 24.0% by ASA 100?mg plain, 100?mg enteric-coated, and 40?mg plain on day 7, respectively. Platelet TXB₂ release was 11?592.0?± 367.5?pg?·?ml^?1 PRP. It was inhibited by 90.1%, 86.5%, and 55.2% by ASA 100?mg plain, 100?mg enteric-coated, and 40?mg plain, respectively. Serum TXB₂ was almost completely reduced on day?7 by 100?mg ASA, but not by 40?mg ASA; serum 6-keto-PGF_1α was slightly, but significantly reduced in all three groups. Urinary 2,3-dinor-TXB₂ excretion was 196.0?±?41.5?pg?·?mg^?1 creatinine at baseline. It was reduced by 80.3% and 79.1% by ASA 100?mg plain and enteric-coated, respectively (each P?<?0.05 versus baseline), but only by 55.4% by ASA 40?mg plain (P?<?0.05 versus both formulations of ASA 100?mg). Conclusions: Our present data show that the plain and enteric-coated formulations of 100?mg ASA are equally effective in inhibiting platelet aggregation, platelet thromboxane production, and urinary 2,3-dinor-TXB₂ excretion rates. In contrast, a very low dose of 40?mg ASA was significantly less effective in inhibiting these indices of platelet activation in healthy human subjects. ASA enteric-coated 100?mg may be a useful alternative to 100?mg ASA (p) in patients with gastrointestinal side-effects, whereas 40?mg ASA (p) may be too low to inhibit sufficiently platelet activity in patients with cardiovascular diseases in whom platelet activity is increased.     

Cyclodextrin-based nanosponges: effective nanocarrier for Tamoxifen delivery

The purpose of the present study was to develop Tamoxifen loaded β-cyclodextrin nanosponges for oral drug delivery. The three types of Tamoxifen loaded β-cyclodextrin nanosponges were synthesized by varying the molar ratios of β-cyclodextrin to carbonyldiimidazole as a crosslinker viz. 1:2, 1:4 and 1:8. The Tamoxifen nanosponge complex (TNC) with particle size of 400–600?nm was obtained by freeze drying method. Differential scanning calorimetry, Fourier transformed infra-red spectroscopy and X-ray powder diffraction studies confirmed the complexation of Tamoxifen with cyclodextrin nanosponge. AUC and C_max of TNC formulation (1236.4?±?16.12 µg·mL^?1 h, 421.156?±?0.91 µg/mL) after gastric intubation were 1.44 fold and 1.38 fold higher than plain drug (856.079?±?15.18 µg·mL^?1 h, 298.532?±?1.15 µg/mL). Cytotoxic studies on MCF-7 cells showed that TNC formulation was more cytotoxic than plain Tamoxifen after 24 and 48?h of incubation.     

Sustained release spherical agglomerates of polymethacrylates containing mefenamic acid: in vitro release,micromeritic properties and histological studies

Mefenamic acid (MA) spherical agglomerates (SAs) were prepared with various polymethacrylates having different permeability characteristics (Eudragit RS 100, Eudragit RL 100 and Eudragit L 100) and also with combination of Eudragit RS 100 and Eudragit L 100 in different ratios. SAs were prepared by spherical crystallization method using ethanol/dichloromethane solvent (crystallization) system. The influence of various formulation factors on the encapsulation efficiency, as in vitro drug release, and micromeritic properties was investigated. Target release profile of MA was also drawn. The yields of preparation and the encapsulation efficiencies were high for all formulations. The shape and surface characteristics of SAs were observed by a scanning electron microscope. The particle sizes are in the range of 0.219?±?0.1 to 0.482?±?0.25?mm (mean ± confidence interval t_95%). In addition, histological studies showed that the administration of MA in SAs containing Eudragit RS/L provided a distinct tissue protection in the stomach and duodenum. Differential scanning calorimetry and X-ray diffraction of powder studies showed that MA particles crystallized in the presence of polymethacrylates did not undergo structural modifications.     

Pharmacokinetics and bioequivalence of two strontium ranelate formulations after single oral administration in healthy Chinese subjects

1. Pharmacokinetics of exogenous strontium (Sr) and bioequivalence of a new oral formulation of strontium ranelate compared with the brand-name drug in healthy Chinese subjects was evaluated.

2. A balanced, randomized, single-dose, two-treatment parallel study was conducted in 36 healthy Chinese subjects. Subjects were randomly allocated into two groups of 18 to receive a single oral dose of test formulation and reference formulation under a fasting state, respectively. Blood samples were collected at 19 designated time points up to 240-h post-dose. Serum concentrations of Sr were quantified by ICP-MS.

3. A total of 36 subjects were enrolled and completed the study. Nine mild adverse events in 6 subjects were reported. The C_max, AUC_0–72?h, AUC_0–t, and AUC_0–∞ of test and reference formulations shown as mean?±?SD were 6.97?±?1.78 and 6.78?±?1.80?µg/mL, 199?±?51 and 187?±?38?µg·h/mL, 303?±?89 and 278?±?54?µg·h/mL, and 337?±?109 and 305?±?60?µg·h/mL, respectively.

4. Two formulations were bioequivalent, and both were generally well tolerated.

     

Mathematical approach for understanding deagglomeration behaviour of drug powder in formulations with coarse carrier

Deagglomeration of cohesive particles in combination with coarse carrier is a key requirement for inhaled formulations. The aim of the project was to propose a mathematical approach to understand aerosolization behaviour of micronized particles alone and in formulation with carriers. Salbutamol sulphate and salmeterol xinafoate were blended separately with fine lactose (ratio 1:4) and fine and coarse lactose (1:4:63.5). Laser diffraction was employed to characterize the powder median particle size. The deagglomeration of micronized materials followed an asymptotic monoexponential relationship. When the coarse lactose was added, the relationship fitted a bi-exponential equation showing an easily and a poorly dispersed fraction. Using model hydrophobic and hydrophilic APIs, this study has demonstrated the utility of an analytical approach that can parameterize deagglomeration behaviour of carrier-free and carrier-based inhalation formulations. The analytical approach provides the ability to systematically study the effect of material, formulation and processing factors on deagglomeration behaviour.     

Development of mucoadhesive floating hollow beads of acyclovir with gastroretentive properties

Abstract

This study aimed at improving the oral bioavailability of acyclovir (ACV) through incorporating it into gastroretentive dosage form based on floating hollow chitosan beads. Hollow chitosan beads were prepared using a solvent free, ionotropic gelation method. The effect of formulation parameters, including chitosan molecular weight and drug concentration, on bead characteristics was studied. The drug containing formulations had yields >70.5?±?0.31%. The entrapment efficiencies for the medium molecular weight chitosan formulations (56.29?±?0.94%–62.75?±?0.86%) was greater than the high molecular weight chitosan formulation (29.21?±?0.89%). The density of all formulations was below that of gastric fluid, the greatest density observed was 0.60?±?0.01?g?cm^?3. Unsurprisingly, the formulations were immediate bouyant to different degrees in both pH 1.2 and pH 6.8 media. In addition, the chitosan beads were all seen to swell in pH 1.2 media and demonstrated mucoadhesive properties. A sustained release profile was observed from the chitosan beads, the developed formulations released drug at slower rates than a marketed ACV oral tablet. The developed system has the dual advantages of being gastroretentive, to increase oral bioavailability and releasing drug in a controlled manner, to reduce the required frequency of administration thereby promoting patient adherence.