Design, development, and technical considerations for dry powder inhaler devices.

The dry powder inhaler (DPI) stands out as a highly patient-friendly and effective pulmonary formulation, surpassing traditional and other pulmonary dosage forms in certain disease conditions. The development of DPI products, however, presents more complexities than that of other dosage forms, particularly in device design and the integration of the drug formulation. This review focuses on the capabilities of DPI devices in pulmonary drug delivery, with a special emphasis on device design and formulation development. It also discusses into the principles of deep lung particle deposition and device engineering, and provides a current overview of the market for DPI devices. Furthermore, the review highlights the use of computational fluid dynamics (CFD) in DPI product design and discusses the regulatory environment surrounding these devices.

Gellan gum-based in situ gelling ophthalmic nanosuspension of Posaconazole.

The formulation and delivery of highly hydrophobic drugs in an optimized dosage form is challenging to formulation scientists. Posaconazole has shown promising action in case studies against fungal keratitis. Biological macromolecules like gellan gum would aid in enhancing the availability of such drugs by increasing the contact time of the formulation. Herein, we propose a transmucosal ocular delivery system of Posaconazole by developing a gellan gum-based in situ gelling nanosuspension. The HPLC method for Posaconazole was developed and validated as per ICH guidelines. The nanosuspension was prepared by microfluidization and optimized by Quality by Design. The gellan gum concentration selected was 0.4% w/v based on the viscosity and mucoadhesion measurements. A greater zone of inhibition of ~ 15 mm was observed for the prepared nanosuspension as compared to ~ 11 mm for the marketed itraconazole nanosuspension. A potential irritancy score of 0.85, considered to be non-irritant, was observed for the developed nanosuspension. Higher drug release of ~ 35% was noted for the nanosuspension compared to about ~ 10% for the coarse suspension. Ex vivo corneal retention studies on excised goat cornea demonstrated ~ 70% drug retention in the tissue. Graphical abstract depicting the central hypothesis of the work.

A triple combination 'nano' dry powder inhaler for tuberculosis: in vitro and in vivo pulmonary characterization.

Inhalation route of drug delivery is the most favorable for pulmonary infections wherein direct drug delivery is desired to the lungs. Tuberculosis is one such infection suffering from poor therapeutic efficacy because of low patient compliance due to high drug dosing and lengthy treatment protocols. The current research work was undertaken to develop a dry powder inhaler (DPI) for administration of three first-line antitubercular antibiotics directly to the lungs to improve the treatment rates. Nanoformulations of isoniazid, pyrazinamide, and rifampicin were prepared, spray-dried to obtain a dry powder system, and blended with inhalation grade lactose to develop the DPI. The DPI was evaluated for its flow properties, pulmonary deposition, dissolution profile, and stability. The DPI possessed excellent flow properties with a fine particle fraction of 45% and a mass median aerodynamic diameter of approximately 5 µm indicating satisfactory lung deposition. In vitro drug release exhibited a sustained release of the formulations. In vivo studies showed a prolonged deposition in the lung at elevated concentrations compared to oral therapy. Stability studies proved that the formulation remained stable at accelerated and long-term stability conditions. The DPI could complement the existing oral therapy in enhancing the therapeutic efficacy in patients.

Comparison of media milling and microfluidization methods for engineering of nanocrystals: a case study.

OBJECTIVE: The article focuses on exploring and comparing two top-down methods, i.e. media milling and microfluidization for the fabrication of nanocrystals of rifampicin (RIF), a poorly water-soluble drug in terms of their potential for generation of stable and efficacious nanocrystals. SIGNIFICANCE: Nanocrystals are often the system of choice for the formulation of poorly water-soluble drugs. The characteristic benefit of nanocrystals lies in their ability to boost the bioavailability of such drugs by enhancing their saturation solubility and dissolution velocity. Nanocrystals can be prepared by either bottom-up or top-down approach. The latter is often preferred due to the feasibility of scale-up and economical nature. Hence, the emphasis is on these methods. METHODS: Stable RIF nanocrystals (RIF NCs) were developed and optimized using media milling and microfluidizer method by incorporating a suitable surfactant/stabilizer. The developed nanocrystals were evaluated for their saturation solubility, in vitro dissolution, solid-state characteristics, morphology, intrinsic dissolution rate, and short-term physical stability. RESULTS: Both the methods were found to be equally efficient in terms of development of stable RIF NCs, while in terms of processing time and efficacy, microfluidization was found to be advantageous. Amorphization and polymorphic conversion were evident based on the results of solid-state characterization. Furthermore, both formulations exhibited an enhanced solubility and faster dissolution velocity. CONCLUSION: Based on the characterization outcomes, it can be concluded that both the top-down technologies could be successfully applied to develop nanocrystals of poorly water-soluble drugs. However, microfluidization was found to outplay media milling in terms of processing time and drug loading.

Performance Parameters and Characterizations of Nanocrystals: A Brief Review.

Poor bioavailability of drugs associated with their poor solubility limits the clinical effectiveness of almost 40% of the newly discovered drug moieties. Low solubility, coupled with a high log p value, high melting point and high dose necessitates exploration of alternative formulation strategies for such drugs. One such novel approach is formulation of the drugs as "Nanocrystals". Nanocrystals are primarily comprised of drug and surfactants/stabilizers and are manufactured by "top-down" or "bottom-up" methods. Nanocrystals aid the clinical efficacy of drugs by various means such as enhancement of bioavailability, lowering of dose requirement, and facilitating sustained release of the drug. This effect is dependent on the various characteristics of nanocrystals (particle size, saturation solubility, dissolution velocity), which have an impact on the improved performance of the nanocrystals. Various sophisticated techniques have been developed to evaluate these characteristics. This article describes in detail the various characterization techniques along with a brief review of the significance of the various parameters on the performance of nanocrystals.

Multidimensional Ophthalmic Nanosystems for Molecular Detection and Therapy of Eye Disorders.

Symptomatic distresses associated with common ophthalmic infections and their persistence, have remained a tribulation with repeated occurrences. Although being a directly accessible organ, traditional therapeutic strategies exhibiting seemingly fruitful outcome in treatment and prognosis of eye disorders call for improvement in disease intervention. This is due to frequent challenges presented by the ophthalmic environment. Contemporary research has addressed these challenges by applying nanotechnology as a central concept in designing more proficient diagnostic and therapeutic systems for eye ailments. Within such nanosystems (dendrimers, aptamers, metal nanoparticles, etc.), bioactive agents, drugs and genetic materials can be entrapped and these form the key elements that act at the biomolecular stage and bestow a high level of efficacy towards eradication of disease causatives and specificity for recognition and capture aiding diagnostic processes. In the current review, we present researched and patented nanocentric technologies as promising tools in detection and treatment of ophthalmic ailments.

Theranostics for cancer therapy.

With over 10 million new cases per year worldwide, Cancer remains one of the most urgent health concerns and a difficult disease to treat. For an effective treatment, improved diagnostic and therapeutic techniques with minimal side-effects are required. Research and development in the areas of nanoscience and nanotechnology promise to provide innovative and more effective approaches for early diagnosis, imaging and therapy. An emerging trend in this direction is Theranostics which represents a combinatorial diagnosis and therapeutic approach to cancer disease and aims to eliminate multi-step procedures, reduce delays in treatment and improves patient care. It offers various advantages like improved diagnosis, tumor specific delivery of drugs, reduced lethal effects to normal tissues etc. Theranostic nanomedicines like nanoshells, plasmonic nanobubbles, quantum dots etc. can be used effectively for achieving these goals. With the advances in nano-imaging and nano-therapy new avenues for the development of effective cancer treatment will be opened.

Microbubbles and their applications in pharmaceutical targeting.

Microbubbles are small spherical gas filled bubbles in the size range of 1-10 microns. Their external coat is made of polymers or phospholipids. In combination with ultrasound, they have been explored as contrast agents for ultrasound and also carriers for drug and gene delivery. In response to ultrasound of lower mechanical index, microbubbles oscillate and vibrate to give a distinct signal in ultrasound imaging. At a higher mechanical index, these microbubbles rupture and break to deliver the drugs or genes enclosed in them or attached to their surface. The behaviour of microbubbles in response to ultrasound is a characteristic of the properties of microbubbles like its shell composition, shell thickness and the density and compressibility of the enclosed gas. Microbubbles have various applications in diagnostic imaging like echocardiography, and imaging of cancer cells, inflammed cells etc. They are also used as a medium for drug and gene delivery. Microbubbles can be further modified by binding specific ligands to their surface which specifically attach to certain cells so that selective action of the microbubbles can be seen at that location of cells.