According to European medicines agency’s- ‘Guideline on Pharmaceutical development of medicines for paediatric use’1; concept of mini-tablets should be explored considering child’s condition and ease of swallowing mini-tablets are tablets with diameter of 3 mm or less.2 Mini-tablets offer flexibility to titer API doses up to 55% of tablet weight and can also be filled in hard gelatin capsules/sachets. There is also provision to dispense from a mechanical mini-tablet dispenser.5 The advantages of minitablets are summarized in a research paper by Biplob M et al.2 Among the benefits described, most significant are 1) ease of swallowing with mini-tablets for pediatric/geriatric populations and 2) dose flexibility so that the dose can be titrated to small increments.
The performance of a dry powder inhalation product heavily relies on the particle size distribution of its components. The size of particles is commonly determined by laser diffraction methodologies. However, since no technique is free of limitations and drawbacks, inevitable off-sets occur between different laboratories. A convenient way to quantify these inevitable off sets between laboratories is the execution of a round robin test series.
In the current Quality by Design paradigm, the development of a pharmaceutical product requires a thorough understanding of the design space to enable the builtin of quality in the product.
In the pharmaceutical industry excipients are added to pharmaceutical dosage forms for multiple reasons. Commonly, they are included to aid the processing or enhance stability and/or bioavailability of a drug in a patient. Excipients do not exhibit a medical function, but are proven essential in both biopharmaceutical and technical aspects. A key attribute of excipients besides functionality is their consistency.
The purpose of this work was to find the optimum balance of excipients microcrystalline cellulose (MCC), anhydrous lactose and partially pregeletinized starch to produce strong tablets yet disintegrating fast. The excipient and concentration optimization is done in terms of maximum tensile strength and minimum friability and disintegration times. This work may provide formulation knowledge by understanding the interaction between each of the three functional excipients.
Lactose and MCC are widely used safe and trusted excipients mainly in oral solid dosage forms. Key excipient suppliers have developed ready to use directly compressible lactose and MCC grades by applying techniques like granulation or drying enabling customers to fatsen formulation development. These highly functional excipients assures fast and stable production when used individually and in combination. The main objective of this study is to evaluate synergistic concentration window for such directly compressible fundamental excipients like anhydrous lactose (brittle ingredient) and MCC (plastic ingredient) in DC tablet.
Main objective of this work is to present an excipient manufacturers view on how to use principles of QbD in the continuous improvement of existing excipient products throughout the production chain, to further increase product consistency.
The excipient of choice for dry powder inhalers (DPI) is lactose monohydrate. It plays an important role in the whole formulation process from bulking the dose chamber in the devices to facilitate dose delivery by the respiratory action of a patient. A number of scientific papers and opinions have been devoted to the specific role of lactose fines and discussion is still ongoing. Commercially, a number of lactose excipients are available with varying amount of fines. In a Quality by Design environment, control of critical attributes of DPI formulations is essential. In this investigation we will demonstrate that, as different sized lactose fines affect different properties, the definition of what we consider ‘fines’ is of utmost importance.
The development of robust and cost effective formulations of moisture sensitive drugs is complicated due to poor flow of drug, variable dissolution rates, and/or instability. Excipients like microcrystalline cellulose (MCC) and lactose with low moisture levels can accelerate their formulation development. The main objective of this study is to show the tabletability performance of low moisture MCC and anhydrous lactose in moisture sensitive tablet formulation.
Knowledge of dwell time sensitivity is very useful especially during scale up of directly compressible tablet formulation. However, very limited quantitativedata is available in the literature on this property. The main purpose of this study was to quantify the dwell time sensitivity of commonly used grades of directly compression lactose (DCL) alone and in combination with microcrystalline cellulose (MCC).
For fast disintegrating tablets, quick disintegration is desired. Sodium starch glycolate (SSG), a cross-linked sodium carboxy methylated (potato) starch, is widely used as superdisintegrant for oral solid dosage forms. The aim of this work was to examine the functionality of different sources of SSGs in developing fast disintegrating tablets of a low-dose model drug.
Microcrystalline Cellulose (MCC) is used in a wide variety of oral solid dosage forms, including tablets, capsules, pellets and others. It is one of the most commonly used diluents in drug formulations. MCC is commonly used in combination with a brittle excipient such as anhydrous lactose in which the benefits of high tablet strength and insensitivity to recompaction are combined to give robust dry granulation formulations.
Lactose plays an important role in dry powder inhalers where it functions as a carrier to aid filling of the powder in the device and fluidization of the powderout of the device1. In general, lactose is present in large excess when compared to the active drug (where drug loads below 1-2% of the formulation mass are common). Subsequently, the powder properties and performance of a formulation can be significantly determined by properties of the lactose carrier. Performance of an inhalation device is determined by the amount of active pharmaceutical ingredient (API) that is delivered to the lung.
The memory of powders for past process history is of high relevance to dry powder inhaler (DPI) formulation. Here the impact of consolidation stresses on formulations with inhalation grade lactose on the DPI performance is tested. Lactohale powders with budesonide filled in capsules with the Omnidose TT and fired from the Cyclohaler were not affected by the filling process.
In vitro testing is a key element in the testing and understanding of dry powder inhalers. The most common excipient used in dry powder inhalers is lactose. Besides the role of lactose as diluent to aid in filling of devices, capsules or blisters, lactose plays an important role during the inhalation event. Here we will discuss two methods to measure the lactose deposited during in vitro testing in the impactor. The first is a wet-chemical method, where lactose is labeled with ammonia in order to allow for colorimetric determination of the content. The second method is based on Raman spectroscopy in order to distinguish between lactose and other ingredients of the formulation.
This article looks at the current level of attention given to carrier lactose for dry powder inhalers (DPIs) and assesses how this attention may affect the future. We believe that further developments will involve closer co‑operation between inhalation grade lactose suppliers, DPI product manufacturers and regulators. This conclusion can be supported by examples of characterization, Quality by Design(QbD) and regulatory developments.
Comparative Dispersion Study of Dry Powder Aerosols of Albuterol Sulfate/Lactose Monohydrate and Disodium Cromoglycate/Lactose Monohydrate Delivered by Standardized Entrainment Tubes
Characterization of Dry Powder Aerosols of Albuterol Sulfate/Lactose Monohydrate and Cromolyn Sodium/Lactose Monohydrate Delivered by Standardized Entrainment Tubes
Most Dry Powder Inhaler (DPI) products are formulated as interactive mixtures of micronized drug (<5μm in size) and larger carrier particles, typically lactose monohydrate. The carrier particles prevent powder aggregation and aid in flow and metering. When the patient actuates the inhaler device, powder is fluidized and enters the patient’s airways. Micronized drug separates from its carrier and is carried into the lung while the carrier particles impact the throat and are cleared. Batch to batch variation of drug and lactose can adversely affect the formulation, leading to inconsistent operation of the inhaler.