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ExploDose® Technology

USA Pharmaceuticals & Sports Science has been creating and formulating quality national brand equivalent and unique products since 1979. Our goal is to create products that offer excellent quality, value and efficacy to help reduce suffering. We offer an extensive selection of formulas and ready-market products. Our chemists strive to stay current with the latest technologies, product trends and ingredients. USA Pharmaceuticals & Sports Science works diligently to produce new and unique products and works closely with our customers to build product lines for increased sales and profits.

USA Pharmaceuticals & Sports Science has over 36 years of experience in contract manufacturing and as one of the largest solid-dose and powder manufacturer in the America, USA Pharmaceuticals & Sports Science can produce:

USA Pharmaceuticals & Sports Science which held major market share positions in a range of analgesics including paracetamol and ibuprofen. The company focused on developing an oral technology which could improve the rate of absorption of oral analgesics to match that of an injection or an oral solution. Research soon showed that in vivo dissolution and gastric emptying were rate limiting steps for the absorption of paracetamol, factors which will affect the absorption of any drug absorbed by passive diffusion. Further research showed that variability in gastric motility and gastric pH were key impediments to in vivo dissolution. Even standard tablets will dissolve quickly if motility is high and the pH suits the solubility of the drug BUT gastric quiescence and an adverse pH to solubility will slow dissolution substantially – leading to slow gastric emptying and slow absorption. It became clear that once the drug dissolved in the co-administered water it reached the small intestine quickly as liquids empty independently of the gastric emptying cycle in both fed and fasted states. Once the drug in solution reaches the small intestine, rapid absorption ensues as the concentration gradient across the small intestinal wall, into the plasma is high. USA Pharmaceuticals & Sports Science believes that its ExploDose® technology solves an important and unrecognized problem, variability in oral absorption kinetics which leads to variability in the timing and extent of peak plasma concentrations. This variability reduces efficacy and delays the mean time to peak effect.

Most drugs do not work for every person or for any one person on every dose occasion. Pain relieving tablets commonly provide acceptable pain relief on only 60% of occasions. The world’s most prescribed migraine tablet provides complete pain relief at two hours on only one quarter of occasions. Research shows that when people take tablets, the peak blood levels of the drug can vary by several hundred percent – a huge amount of variation given the high value placed on consistency and product effectiveness. A patient’s gastric pH and motility changes continually throughout the day according to the intake of food and the volume and type of food eaten. If a patient takes a tablet at the time when they have high gastric motility and a gastric pH which favors the solubility of the drug, the drug dissolves from the tablet and empties into the small intestine quickly leading to rapid absorption and high blood levels of the drug.

As almost all drugs area absorbed through the intestinal wall, not through the stomach, it is only when the drug dissolves rapidly and empties from the stomach rapidly that rapid absorption from the small intestine can occur. If a tablet is taken when the stomach is resting (low motility) or at a pH not favorable to drug solubility the drug will not dissolve quickly and empty into the intestine, resulting in slow absorption and low peak blood levels. Slow absorption is a problem, as low peak blood levels may mean that the drug fails to achieve full effect on that occasion. Slow absorption will also result in delayed onset of action.

ExploDose® technology enhances oral delivery performance so that the drug will reach effective levels on most occasions on which it is taken. The technology enabled tablet is intended to be swallowed whole with a glass of water. The technology works by utilizing inert tablet ingredients which drive extremely rapid dissolution of the drug, blowing the tablet apart and creating the right pH for optimal drug solubility in the patient’s stomach. Dissolved drug empties into the small intestine where the high drug concentration drives absorption and then distribution in the body. The technology takes advantage of the fact that liquids empty from the stomach rapidly whether the patient is fasted or has recently ingested food. For most drugs this new formulation approach will mean rapid absorption independent of gastric pH and motility at the time of dosing, leading to both improved effectiveness and earlier onset of drug action. It provides an unsurpassed solution with the potential to revolutionize how drugs are administered across the world. Compared to existing technology, based on the evidence to date, USA Pharmaceuticals & Sports Science believes that 90% of patients will achieve high blood levels of the drug earlier (20-30 minutes after dosing compared with 1 hour or more for standard tablets and orally disintegrating tablets / ODT’s) and that for many drugs the technology will achieve an increase in effective dose occasions of between 50 and 100%. We believe ExploDose® proprietary system will provide the desired delivery profiles for most formulators. As examples Catalent has established its Zydus® technology as a leader in orally disintegratable tablets and Elan Drug Technologies established its oral controlled release (OCR) technology as a leader in controlled release. ExploDose® is positioned to set a new standard for consistent oral absorption.

ExploDose® uses a customized mixture of acid and base to maximize drug solubility and to generate stirring energy through effervescence which occurs when available acid and base react in the presence of water. These effects drive very rapid in vivo dissolution which in turn drives gastric emptying as the dissolved drug empties in the co-administered water. The resultant concentrated bolus of drug in solution provides a high concentration gradient to drive rapid absorption across the intestinal wall into the plasma and rapid distribution to the site of action. Consistent rapid absorption provides for high peak plasma concentrations (Cmax) and early peak plasma concentrations (Tmax). Short Tmax will usually mean reduced time to onset of effect and reduced time to peak effect. Consistent high Cmax reduces the probability of low or sub-therapeutic plasma concentrations which may lead to sub-optimal efficacy.

Data from a study in 25 fasted healthy subjects 19 demonstrated significantly faster absorption with two fast dissolving ExploDose® paracetamol formulations, compared with Tylenol® Extra Strength Rapid Release Gels (McNeil Consumer, US) Tylenol®: 83 and 96 % subjects receiving Surge Dose® tablets exceeded the reported minimum therapeutic level for paracetamol of 10 µg/mL in the first 15 min compared with only 20 % subjects receiving Tylenol®

16 % subjects taking Tylenol® never reached 10 µg/mL indicating sub-therapeutic dosing compared with only 4 % for ExploDose® formulations. Median Tmax values for the Explode Dose® formulations were 17 and 25 min compared with 45 min for Tylenol® -- ExploDose® AUC0-30 values indicated 3 times as much absorbed in the first 30 min compared with Tylenol.

Fast dissolving ExploDose® tablets

USA Pharmaceuticals & Sports Science has shown that experimental ExploDose® tablets containing 200 mg ibuprofen as the free acid or sodium salt demonstrate significantly faster dissolution than commercial Advil® tablets (final pH 2.3) and liquid filled softgel capsules (final pH 2.3) under a range of conditions that simulate adverse physiological conditions. In vitro dissolution exceeding 80 % within 3 minutes was achieved.

Dissolution from the ExploDose® tablet exceeds 70 % within 3 min compared with negligible dissolution from the Advil® tablet. The Advil® liquid filled capsule shows steady dissolution after a lag time of around 4 min as the solubilized drug is released from the capsule after rupture. The ExploDose® tablet increases the final pH to 5.8 which is sufficient to increase the drug solubility and increase its rate and extent of dissolution.

Comparative dissolution profiles in water, a neutral pH medium that also simulates, but underestimates, the fed state as a result of the lack of buffering. In the absence of acid, the Explo Dose® formulation demonstrates its fastest and most extensive dissolution exceeding 80 % in 3 min. By comparison, the commercial caplets and the liquid filled capsules show negligible dissolution highlighting the value of the pH-controlled activated ExploDose® dissolution. The only commercial product that demonstrated significant dissolution when the stirring speed was increased to 200 rpm after 20 min was the Advil® liquid capsules. These contain solubilized ibuprofen which remains dissolved and disperses in the water once the capsule ruptures.