New strides in formulation development and technologies

5/16/2009

A bulk drug on its own is generally of little use to the patient. Patients require the drug in a form they can use effectively with as little inconvenience as possible.

A look into the crystal ball; indicates evolution of pharmaceutical practices: Empiricism and art (50’s); to physical and technology (50’s- 60’s); to technology assessment- bio-pharmaceutics/ pharmaco-kinetics (60’s- late 70’s); to drug delivery system and targeting strategies ( 70’s – 80’s); to formulation with a view towards the molecular levels (90’s).

A snapshot in history shows that “formulation development“ has now been re-christened as “ formulation technology” and circumvents excipients, their standardization, machinery- its design and automation, bulk actives, product recipe, process of manufacture and pack material development etc. However, the millenium 2000 has presented some major challenges to the formulation scientists -

1. Rapid introduction of new chemical entities.
2. Development of strategies for their delivery presentations.
3. Product patent scenario in most of the countries globally due to WTO.
4. Rush to be first- to market and beat competition.

Quite a few drugs originating from the biotechnology route have been introduced.

The late 80’s and 90’s had witnessed conception of a host of dosage forms such as sustained release (SR) controlled release (CR), osmotic and iontophoretic devices , transdermal systems, lyophilized parenterals and targeted drug delivery by parenteral route etc. however , oral ingestion has always been accepted as a delivery of choice.

So what is new in pharmaceutical dosage forms ? what is being well-discussed about for over 10 years now, but still is considered ‘novel’ by the pharmaceuticals research communiy. I have penned here majority of the information on current Advances in dosage form delivery :

Advances in oral delivery systems-

Attempts to develop a single dose therapy for the whole duration of treatment has focused attention on SR and CR drug delivery systems (DDS) for oral (parenteral as well as transdermal) systems , yet another approach being drug targeting.

“ Sustained release” describes a DDS with delayed therapeutic action and sustained duration of therapeutic effect. Controlled release implies a predictability and reproducibility in the drug release kinetics.

The design of CRDDS accounts three important criteria viz. drug, delivery and destination. CR dosage form therefore have been further classified as pulsatile- , time- extended-release etc. Though much research has already been conducted to develop CRDDS very few systems which are retained in stomach for long time have been developed so far. These systems mainly consist of ;

1. Swelling and expanding systems
2. Floating and inflating system and
3. Bio adhesive systems.

i.        Swelling and expanding systems: one way to retain a dosage form in the stomach is by increasing its size. The stomach discharges its size. The stomach dischares its content through the pulorus into intestine. If the dosage form attains a sizelarger than that of the pylorus. Ofcourse only when it has reached the stomach, it can be retained for a long time. Drug dispersed into such swelling polymer matrices now acts as a miniature constant drug flow pump.

ii.      Floating systems: A floating dosage unit is useful for drugs acting locally in the proximal gastrointestinal (GIT) or for those which are either poorly soluble or unstable in intestinal fluids. The floating properties of these systems help in protracted gastric retention. Floating systems exhibit controlled release as well as much lower peak gastric juice drug levels than conventional systems. The low dosages over a prolonged period of time help in reducing GIT irritation.

iii.    Bio/Muco-adhesive systems: Mucosal DDS provide intimate contact between a dosage form and the absorbing tissue which results in high flux through the absorbing tissues as well as increase in the total permeability of high molecular weight, moieties such as peptides and proteins. These systems provide both CR and tissue targeting of drugs.

We shall discuss controlled and mucosal delivery systems in great depth as separate post as a series. Hence, we park these topic here and move on with discussion on other delivery forms in the coming days ...