Effervescent dry powder for respiratory drug delivery

by Leticia Ely , Wilson Roa , Warren H. Finlay , Raimar Lo¨benberg

In recent past pulmonary drug delivery has become a major interested involving systemic drug absorption and treatment methods for diseases such as diabetes mellitus, pain relief, cystic fibrosis, asthma, lung cancer, and tuberculosis. Delivering drugs through pulmonary system comes with challenges. These are tackled with the help of nanoparticles, aerosols and delivering drugs in the form of dry powder.

Use of nanoparticles in pulmonary drug delivery helps bypass mucocillary clearance, phagocyte clearance and translocation by epithelium cells. Drawbacks include the size of the nanoparticles that limit lung deposition, limited sedimentation lead the aresole to be cleared by lung quicly after inhalation. Aerosoles are incorporated with carrier particles and the increase in size helps increase the amount of drug deposition to the lungs.

Effervescent drug delivery has been widely used in oral drug treatments, especially for treatments of stomach distress, vitamin supplements and analgesics. However, the authors states by year 2006 none has attempted use of effervescent formulations for treatment of pulmonary drug delivery. Therefore this study is the first attempted to investigate the suitability of effervescent technology along with nanonparticles for pulmonary drug delivery.

Polybutlycyanoacrylate (PBC) nonoparticle and ciprofloxacin hydrocholiride hydrate (CHH) are used as the model substance in this study to investigate suitability of active release mechanism of effervescent for pulmonary drug delivery. The new effervescent formulation was tested by comparing it with dispersion time of lactose particle carriers.

Both PBC nanoparciels and CHH nanoparticle was prepared using standard procedure as explained in brief in the article. The derived particle were then tested for loading efficiency by dissolving lactose or effervescent powder in water and analyzed using UV spectroscopy at 271nm before and after loading. Dissolved drug content was then calculated with the help of calibration curve and liner regression. To tag the particles with flourcent labeling, 7 ml of suspension of PBC was added to 7% lactose containing solution or to 7% lactose solution with either PEG 6000 and L-leucine or 7% lactose solution with an effervescent solution contacting PEG 6000 and L-Leucine. The solutions were then spray dried under standard conditions used in this study.

The particle size was determined using the photon spectroscopy. Mass, median diameter ( MMA) was determined with help of Mark II Anderson cascade Impactor and with new high efficiency inhaler. Sample were also investigated using confocal laser microscopy and scanning electron microscopy . Different compositions of the powders were tested and spray dried to analyze an appropriate size that will help pulmonary delivery.

To formulate a novel effervescent formulation different concentrations of citric acid, and carbonates in different rations of 50% sodium carbonate, 50% sodium bicarbonate was analyzed in tablet formulation. Two components in an aqueous environment are shown in the following formulation.

R–COOH þ XHCO3 H2O R–COOX þ CO2 þ H2O

As seen effervescent formulation releases carbon dioxide, when disintegration is increased and absorption is increased the phase transition between solid phase and gas phase result in an increase of volume and drug dissolution. The basic effervescent formulation contains citric acid, water and sodium carbonate, since this formulation has to be spray dried in order to be used for pulmonary delivery the Ph of solution was increased at 8 by adding ammonia. To active the expected MMD and particle size polysorbate 80, L-leucine and PEG 6000 were added to the basic formulation along with different amounts of lactose were added.

Change in amounts of lactose resulted in changes in size and morphology of the career particles. Smaller particle sizes were achieved increasing the lactose and visa versa. They were dense and spherical in shape.

The particle sizes data indicates by lactose was found to be 73.38 +/-13% and for powders containing the L-leucine/PEG 6000 effervescent formulation was 68.55+/- 23.90%, therefore the researchers conclude using PEG 6000 powder would be the most ideal for formation of inhalable particles. Comparison of the releases of drug from drug ciprofloxacin( poorly water soluble) was compared between lactose particles and effervescent formulation. Results indicated effervescent carrier particles released 56+/-8% while lactose particle released 32+/-3. The significance was noted at t-test, P < 0.05.

Polybutylcyanoacrylate nanoparticles were also compared with lactose and effervescent formulation. Four different powders with constant of L-lucin and PEG were created to test the effervescent formulation. Data indicated there was significant increase in particle size P < 0.05 if only lactose was used but when lactose contained PEG and L-Leucin no statistical different was observed in particle sizes.

Effervescent property of carrier particle was tested by exposing to water. Data indicated that nanoparticle was actively distributed in the gas bubbles. When effervescent powder was dispersed in water immediate gas bubbles and dispersion was observed.

A new effervescent formulation was formed for the model drugs. The formulations formulated including lactose containing L-leucin and PEG 6000 was able to release nonpartiles seem to have been better compared to career particles made of just lactose by reducing agglomeratiotion and had better active releases. Results indicted releases of nanoparticle were affected by both the effervescent formulation and coic of excipients used. The force made by the effervescent reaction helped disperser the nonparticle efficiently and reduced particle aggregation and increase disintegration and drug dissolution. Researches also state more studies are needed to determine if the effervescent formulation was inhalable. With further studies the effervescent carrier particle could possibly be used for number of drug delivery to the lung with better efficient compared to the conventional carrier particles.

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One response

  1. Prof Waqar Ahmed | Reply

    Please add reference in full to the journal, volume number and page numbers etc to all summaries

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