The efficacy of any drug is significantly impacted by its mode of delivery[6]. Innovative approaches in drug delivery strategies from a patient-centric standpoint could be a key accelerant for maximizing patient outcomes [21].
One such patient compliant drug delivery system is the orally disintegrating tablets (ODTs). The fast-melting, mouth-dissolving and rapid-disintegrating features of ODTs make it increasingly popular among children, the elderly and patients with difficulty in swallowing. Apart from benefitting the patients, ODTs are a boon for pharmaceutical manufacturers[10]. As a drug’s lifecycle management determines its financial success, it is ever important for drug developers to implement carefully considered life-cycle management programs[11]. Formulating ODTs for existing drugs is a cost-effective way to extend a drug’s life cycle and infuse a new life to the existing brand[4].
The proprietary ODT platform technology used by InstaPill® can be used to develop gelatin free, flavoured and highly palatable ODTs with a typically high disintegration speed. The InstaPill® ODT technology platform has the operational feasibility to design alternatives for injectable medications, such as immunotherapy, vaccines as well as therapeutics for neurological disorders and combination products.
InstaPill® supports the design and development of ODTs from Target Product Profile (TPP) to scale up and validation on our fully automated line for product launch. With a disintegration time of a few seconds on the tongue, InstaPill® ODTs deliver maximum patient acceptance, compliance and convenience.
The strategic development of InstaPill® ODTs is based on the following five key points:
ODT-technology:
A versatile drug-delivery platform ideal for developing ODTs for a wide range of therapeutics including Rx drugs, OTC drugs, veterinary medications and line extensions. The InstaPill® technology platform manages the unique properties of each drug molecule with flexibility and delivers compelling solutions for dosage convenience,thereby providing a competitive market advantage.
Lyophilization:
Oral Lypohilisates demonstrate a faster disintegration in the oral cavity versus standard compression ODTs. InstaPill® uses lyophilization to entrap the active pharmaceutical component in a highly porous matrix. When InstaPill® is placed in the oral cavity, the porous matrix promotes the penetration of saliva leading to disintegration at an accelerated rate without any agitation[19].
Gelatin-free:
Many patients unwittingly consume animal gelatin in prescribed drugs. This may often hurt the sentiments of the patients and lead to non-adherence to the prescribed medications. With the growth of Veganism and Vegetarianism in addition to many cultures and religions avoiding animal-derived foods, InstaPill® manufactures gelatin-free, vegan friendly ODTs that would be appropriate for all patient populations[18].
Taste masking:
Palatability-taste, aromatics and texture is critically important to the successful administration of many oral drugs. Palatability also has an influence on the success of drug therapy. A marketed sublingual tablet containing dimenhydrinate received negative feedback from consumers for its bitter taste, numbing sensation in the mouth and gritty texture. InstaPill® optimized the flavour and palatability of this dimenhydrinate ODT to meet consumer demands.
Convenience:
InstaPill® ODTs target a wide range of therapeutic areas that demand a rapid onset of action including pain management, anti-histamines, anti-emetic, anti-psychotics and anti-convulsants. InstaPill® ODTs offers the possibility of sublingual or buccal absorption of suitable molecules thus promoting a rapid action of the drugs and may evade first-pass metabolism.
The InstaPill®, a proprietary drug delivery technology platform of Tenshi Kaizen offers automated operations to improve speed, accuracy, and quality and GMP compliance manufacturing of ODTs. Once the fully automated commercial line is installed in H2 2022, InstaPill® produce will increase its capacity from approximately 70 million to 270 million ODTs annually, ensuring a consistent supply.
Using QbD and DoE principles InstaPill® designs and develops robust formulation and process technology for lab and exhibit-scale manufacturing as well as scale-up including clinical supply. Relevant drug molecule characteristics are identified and formulation experiments are prepared under different processing conditions during the proof-of-concept evaluation. Pre-formulation studies, API and formulation characterization are conducted throughout the development cycle to support regulatory filings.
The development of ODTs by lyophilization techniques is advantageous as it is compatible with a wide range of complex active biological agents such as attenuated viruses, therapeutic proteins and complex allergen extracts used in immunotherapy[17].
Lyophilized ODTs are advantageous over ODTs produced by the compaction of water-soluble excipients. Compression often leads to very low porosity inhibiting the penetration of water and increasing disintegration time.The liquid bulk formulation is easily dosed and processed directly into lyophilised ODTs in the primary blister packaging[13].
The InstaPill® technology platform has the potential to develop lyophilized ODTs with doses up to 200mg for insoluble APIs and 20mg for soluble APIs. InstaPill® is equipped with the latest models of lyophilizer at different working ranges from lab and pilot scale to fully automated commercial scale. With expertise in optimizing lyophilization cycles, InstaPill® strategically seeks to reduce the manufacturing cost of lyophilized ODTs without compromising the quality.
In Lyophilised ODT composition, excipients with the abilities to dissolve, rapidly absorb water and swell to yield pressure for disintegration are highly desired. For the last 30 years, Gelatin has been a preferred polymeric binder for ODTs. The gelatin glues all the crystalline particles (i.e., drug substance and fillers) together in the final ODT, while mannitol adds rigidity ensuring that the freeze-dried tablet is robust for transport and handling.
But, a study by Vissamsetti et. al. in 2012, showed that 88% of the study population following a restricted diet responded that they would prefer to take drugs containing only vegetable products. Only one in 10 answered that medications containing gelatin did not matter to them. More than half the participants would take a drug containing an animal product if no other alternative was available[15].
Continuous improvements in the ODT compositions are done to enhance the suitability of ODTs for a wider patient population. Non-gelatin binders like polyvinyl alcohol (PVA) have been researched as not jeopardizing the stability, efficacy, safety and rapid disintegration time of the ODTs[14]. The InstaPill® platform uses Pullulan as a structure former which is a sustainable polysaccharide produced by a fungus from plant starches. Pullulan has Generally Recognised as Safer (GRAS) status in the US and in as an accepted food additive E1204 in Europe. InstaPill® demonstrates TSE compliance thereby ensuring that the ODTs are safe for human and animal consumption.
Studies revealed that the unpleasant taste of antibiotics is consistently cited as an obstacle to adherence and should therefore be a key consideration in the management of all common pediatric infectious conditions[8]. The inherently bitter taste of most active pharmaceutical ingredients poses a key challenge for developers to make oral dosage forms taste pleasant. Taste masking is a method used to improve not only the taste of bitter APIs in formulated drug products but also the texture (smooth vs. gritty) to ensure the overall acceptability of medications to patients.
Oral Lypohilisates with their rapid disintegration on the tongue means rapid exposure of the drug substance to the taste receptors of the tongue. It is therefore essential during InstaPill® development to optimise the flavour and sweetener to improve the palatability of its ODTs. With extremely bitter compounds it may be necessary to complex the drug with beta-cyclodextrins or ion exchange resins to reduce the availability of the drug in saliva. By using the InstaPill® platform four formulations were developed, each utilizing optimized sweetener and complexation systems, to mask the taste. Despite no change to pharmacological profiles, improved palatability was established as a key milestone among consumers in accepting the product.
Among the general population, the prevalence of oropharyngeal dysphagia varies between 2.3% and 16% and is much higher in geriatric patients and individuals with neurological disorders[12]. Elderly patients with dysphagia often find themselves in an unpleasant position as they require a large number of medications but have swallowing difficulties. Additionally, delayed transit from mouth to stomach lead to premature drug release and drug degradation, eventually reducing bioavailability. The InstaPill® ODTs are reconstituted with saliva to a very small volume of suspension which is then very easy to swallow which is highly favourable for dysphagia patients.
Adverse swallowing events (ASE) including choking, spitting, coughing, gagging, vomiting and expelling a crushed tablet in a “cloud” of powder are common among pediatric patients. The results of a study by Kernell et.al. showed that out of 1677 children, 14.8% had at least one of the aforementioned ASE- even with crushed tablets or dissolved tablets. ASE such as spitting, coughing prompts a reduction in dose with an ambiguity of the exact dose that is ingested[5]. The taste-masked InstaPill® ODTs disperse in the mouth instantly resulting in a very small volume, easy to swallow suspension making it a highly convenient oral dosage form for pediatric patients.
During travelling, there is an increased chance of missing a dose due to the inappropriateness of the situation or lack of edible water. A missed or delayed antiarrhythmic or anti-epileptic dose can have catastrophic consequences on the patient. Certain antipsychotic and long-acting insulins have a significant loss of therapeutic effect when a dose is missed or delayed [2]. InstaPill® ODTs are administered without water and are blistered packaged making it easily portable without any degradation in its stability.