Six Ways to Test the Physical Properties of a Tablet

Transforming a formulation into a successful solid dose tablet is a complex process that involves many considerations. Time and raw materials are both valuable and must be saved wherever possible in the production process, and getting production right in the early stages is crucial to prevent expensive faults and tablet defects in the downstream production process.

During compression, the ingredients can have a large effect on physical factors. For example, abrasiveness, moisture content and particle size all affect compressibility. Considerations must also be made of the properties of the finished product.

During their manufacture, tablets are subjected to a great deal of physical abuse within the hopper in which they are spun. During this time, chipping may occur. The extent of this depends on tablet hardness. It is undesirable in terms of product quality and is also a potential health risk to the consumer.

Mucosal Delivery: Measuring Product Texture

MUCOSAL DELIVERY

Mucoadhesion is the process by which a drug delivery device is designed to stick to a part of the gut or other mucosae (buccal cavity, nasal, rectal and vaginal), thus delivering drug to a precise site in the body for an extended period. 
 
This gives more effective treatment of some diseases and can also protect drugs from some of the harsh conditions in the body. Mucoadhesive drug delivery systems are used to treat several conditions in the mouth and have been investigated as treatments for stomach ulcers and cancer. The majority of infections affecting man and animals take place or start in mucous membranes. The ability to retain pharmacologically-active agents for extended periods of time on any mucosal epithelium, including those of the nose, mouth, rectum or vagina confers several potential therapeutic advantages.

Transdermal Delivery: Measuring Product Texture

TRANSDERMAL DELIVERY

Transdermal drug delivery as a route for systemic drug administration is currently one of the advancing areas in drug development research.

This is particularly true for the delivery of such drugs as opiate painkillers, birth control, nitroglycerin for the prophylaxis of angina, nicotine for smoking cessation therapy, testosterone for the correction of male hypogonadism. 

The skin route for systemic drug delivery is especially attractive to formulators, as this integument is the most readily accessible organ of the body. Clinicians are increasingly recognising the advantages of controlled continuous intravenous infusion of drugs, such as the avoidance of hepatic metabolism and the maintenance of a constant therapeutic level in the body, that can be obtained by the use of the skin as a portal of drug delivery, without the risks and costs of intravenous therapy.

Developing dermal, transdermal and mucoadhesive delivery systems

INTRODUCTION

Developments in transdermal, dermal and mucoadhesive drug delivery methods are paving the way to the future of systemic drug administration.

As skin is both the largest and most accessible organ in a human body, pharmaceutical manufacturers are keen to take advantage of it as a drug delivery platform.
The transdermal route helps to reduce the risks and costs of intravenous therapy that can be both traumatic and intrusive.

Transdermal controlled release (CR) systems usually combine a therapeutic component with an adhesive formulation that ensures a continuous delivery of the active ingredient through unbroken skin at a constant absorption rate. Skin adhesion and drug compatibility determine the efficacy of transdermal applications.

Parenteral Texture Control: Rectal Delivery Products

RECTAL DELIVERY

Although administration via the peroral route is the most commonly targeted goal of new drug and dosage form research and development, oral administration is not always feasible or desirable.

The potential for oral dosage form development is severely limited for active agents that are poorly absorbed in the upper gastrointestinal (GI) tract and unstable to proteolytic enzymes. Some agents cause local stomach or upper GI irritation or require doses in excess of 500mg. 

Additionally, treatment of some diseases is best achieved by direct administration near the affected area, particularly with diseases involving anorectal tissues. Although oral administration can be used for drugs targeted for some of these diseased tissues, exposure of the entire body compartment to the administered drug is inefficient and can lead to undesired adverse effects.

Parenteral Texture Control: Vaginal Delivery Products

VAGINAL DELIVERY

The vaginal route of administration offers a promising option for local and systemic delivery of drugs.

Suppositories, creams, gels and tablets are commonly used vaginal drug delivery systems. These conventional vaginal formulations, however, are associated with limitations of poor retention, leakage, and messiness, thereby causing inconvenience to users. 

To overcome these limitations, formulations that adhere to the vaginal mucosa for a sufficient period of time need to be developed. Bioadhesion and retention are desirable characteristics of a vaginal formulation to achieve desired efficacy. These properties can be built in during formulation development by the use of bioadhesive polymers and tested by similar methods to those already discussed for bioadhesion. The limitations have also necessitated the development of other novel drug delivery systems.

Parenteral Texture Control: Ocular Delivery Products

OCULAR DELIVERY

Treatment of some diseases is best achieved by direct administration near the affected area, particularly with diseases involving ophthalmic, optic, dermal, oral cavity, and anorectal tissues.

Ocular drug delivery is an interesting and challenging opportunity for pharmaceutical development. The eye is protected by a series of complex defense mechanisms, which usually result in poor bioavailability of drugs administered via the ocular route. These include tear production and the blinking reflex in addition to short residence time and reduced drug permeability.

Parenteral Texture Control: Parenteral Delivery Products

PARENTERAL DELIVERY

Developments in injectable depots and implants are driven by a desire to decrease the necessity for frequent medication.

Incorporating polymer technology for slow, long-term release, this route is best utilised for the treatment of chronic conditions, such as heart disease and pain management. Hip or knee cap replacements are susceptible to infection following surgery.

A preventative approach could be for the doctor to leave behind an implant that could deliver an anti-infective agent and disintegrate with time. These devices give localised, high-concentration delivery, and by tuning the ratio of drug load to polymer the required release rate can be optimised, over two days or two months.

Parenteral Delivery: Under Control

INTRODUCTION

The latest craze to sweep the pharmaceutical industry is one of controlled-release drug delivery systems. 

This controlled release can be systemic (generally via the bloodstream), as is generally the case for oral preparations, or act specifically at the site of greatest benefit (for example, in implanted devices) and these dosage forms are defined as preparations that modify the rate and/or the time and/or site of release of the active ingredient, in order to achieve specific therapeutic objectives which cannot be achieved with conventional dosage forms similarly administered.

Viscoelasticity in the Pharmaceutical and Cosmetics Industries

Many pharmaceutical and cosmetic products have viscoelastic properties that can be measured using a Texture Analyser.

Pharmaceutical tablets show viscoelastic stress-strain behaviour when the powder compact is being loaded and unloaded, and this behaviour continues once the load has been fully removed. This can cause problems for tablet manufacturers such as capping, when either the upper or lower part of the tablet separates from the main body when ejected from the press or during the handling process. 

Viscoelastic properties are functions of the compression conditions as well as the formulation. It is important to investigate every instance of capping to ensure the problem is not repeated (which is very costly) and to measure the viscoelastic properties of new formulations before they reach the mass manufacturing stage. 

Novel Oral Dosage Forms : Granules, Sprays & Sachets

GRANULES
 
Orally disintegrating granules (ODG) score highly in regard to ‘opening the packaging’ and ‘integration into everyday routine’.

They are already available for allergy and pain relief. In addition to those ODGs suitable for adults, singular paediatric 4mg granules are suitable for children aged 6 months to 5 years. The granules can either be given directly into a child's mouth, or mixed with a spoonful of cold or room-temperature soft food (eg apple sauce, ice cream, carrots or rice). They can be taken either with or without food, increasing their popularity from those looking for easy administration.

Novel Oral Dosage Forms : Capsules

CAPSULES

Liquid-fill formulation is one of the fastest growing sectors of the drug delivery market, increasing at a rate of 30% per annum. 

This is due to the number of highly potent chemical and biological drugs moving through development pipelines today – particularly for cancer treatments – but in fact, encapsulated products, such as fish oils, have long been popular as vitamin, health and performance supplements. 

Unlike many other forms, capsules mask taste and odour and allow for quick speed-to-market, yet they require less excipient. Their versatility allows for a multiplicity of branding options in terms of colour, size and printing/graphics. And of course, they are smooth, easy-to-swallow and are suitable for almost any dosage strength.

Novel Oral Dosage Forms : Pastilles/Lozenges

PASTILLES/LOZENGES

While altering oral tablets to create formulations suitable for children has long been a part of paediatric healthcare, it is clearly a less than ideal option. 

Pastilles/Lozenges represent oral medical preparations consisting of sugar and gum that have solidified and are meant to be consumed by light chewing and allowing them to dissolve in the mouth. This makes them a popular choice for children, as they are easy to ingest and integrate into daily routines. In addition, they are simple to formulate, with interesting flavours, and their texture is more appealing to this age category for trouble-free administration. They are usually used to medicate the mouth and throat and for the slow administration of vitamins, indigestion or cough remedies. 

Novel Oral Dosage Forms : Films

FILMS

Thin-film drug delivery has emerged as an advanced alternative to the traditional tablets, capsules and liquids often associated with prescription and OTC medications. 

Similar in size, shape and thickness to a postage stamp, thin-film strips are typically prepared using hydrophilic polymers for oral administration, with the user placing the strip on or under the tongue or along the inside of the cheek where saliva serves to rapidly dissolve the dosage form. 

This drug delivery option also allows the medication to bypass the first pass metabolism, thereby giving the medication significantly more bioavailability than conventional tablet dosage forms. Films alleviate the danger/fear of choking, are easy to handle and administer, have a pleasant mouthfeel and taste and are straightforward to manufacture. They offer the combined advantages of ease and convenience of dosing in the absence of water, anytime, anywhere.

Novel Oral Dosage Forms : Fast-Disintegrating Tablets

FAST-DISINTEGRATING TABLETS

Coming up with novel ways to deliver drugs is key to maintaining profitability.
One approach is to use technologies such as mouth-dissolving tablets or wafers, also known as fast melt, fast dissolving or orodispersible. 

The demand for solid dosage forms that can be dissolved/suspended in water, chewed or rapidly dissolved in the mouth is particularly strong in the paediatric and geriatric markets, with further application to other patients who prefer the convenience of a readily administered dosage form. 

Novel Oral Dosage Forms : Introduction and the Requirement for Quality

Testing the alternatives to traditional tablet-form medications
 
Oral drug delivery represents the largest share of the pharmaceutical market, accounting for approximately 90% of all medicines prescribed. 

The oral route remains the perfect one for the administration of therapeutic agents, due to the general simplicity and cost-effectiveness of the therapy, the accuracy of dosing, the avoidance of pain and the ability to self-medicate. Whilst it is considered the most traditional and easiest route of delivery, it is – perhaps surprisingly – not always the most user-friendly, for a number of reasons.

Keeping an eye on the quality of Ocular Delivery Products using Texture Analysis

Treatment of some diseases is best achieved by direct administration near the affected area, particularly with diseases involving ophthalmic, optic, dermal, oral cavity, and anorectal tissues.

Ocular drug delivery is an interesting and challenging opportunity for pharmaceutical development. 

The eye is protected by a series of complex defence mechanisms, which usually result in poor bioavailability of drugs administered via the ocular route. These include tear production and the blinking reflex in addition to short residence time and reduced drug permeability. The drug bioavailability can be enhanced either by providing prolonged/sustained delivery to the eye or by facilitating transcorneal penetration. 

Texture Analysis in Action: the Powder Compaction Rig

Powder Compaction Rigs:
Low Tolerance (left); High Tolerance (right)

The Stable Micro Systems POWDER COMPACTION RIG is available in two variants.

The High Tolerance Powder Compaction Rig (A/PCRS) is suited to high force applications where the punch/die clearance is critical; this fixture is auto-aligned using a universal adapter.

The Low Tolerance Powder Compaction Rig (A/PCR) is suited to other powder compaction applications such as assessing granule friability, where the punch/die clearance is less critical.

Texture Analysis in Action: the Tablet Disintegration Rig

The TABLET DISINTEGRATION RIG* (A/TDR)

A thorough analysis of disintegration behaviour is vital for the formulation of new fast-melt tablets (FMTs) to ensure reliable and consistent drug release.

The tablet or wafer has to be resilient enough to endure manufacturing and shipping, yet release sufficient disintegrants to deliver an optimum dissolution rate. The Tablet Disintegration Rig facilitates reliable assessment of the mechanical properties of FMTs.

Ensuring consistent quality in Rectal Delivery Products

Although administration via the peroral route is the most commonly targeted goal of new drug and dosage form research and development, oral administration is not always feasible or desirable. 

The potential for oral dosage form development is severely limited for active agents that are poorly absorbed in the upper gastrointestinal (GI) tract and unstable to proteolytic enzymes. Some agents cause local stomach or upper GI irritation or require doses in excess of 500mg. Additionally, treatment of some diseases is best achieved by direct administration near the affected area, particularly with diseases involving anorectal tissues. 

Although oral administration can be used for drugs targeted for some of these diseased tissues, exposure of the entire body compartment to the administered drug is inefficient and can lead to undesired adverse effects.