"Amoxicillin SR Formulation" is a perfect example of a paper on drug therapy. For so long Helicobacter pylori (H. pylori) has been a common pathogenic bacteria that highly damages the epithelial cells of the GIT especially in the duodenum and the stomach. Its existence in the gut results in gastric adenocarcinoma, chronic gastritis, gastric and duodenal ulcers. The α -amino-hydroxybenzylpenicillin is a semi-synthetic that is active against most bacteria including the H. pylori. It is from the aminopenicillin class and, therefore, has an amino group that is bactericidal to both the gram-negative and gram-positive bacteria.
To minimize the harm and increase the effectiveness of amoxicillin the idea of incorporating the delivery systems came up. The sustained release of amoxicillin was then adopted to reduce the costs incurred while using large doses of amoxicillin at higher frequencies since maintaining the therapeutic drug concentration in the systemic blood for a longer duration was possible with sustained release (Arora, Gupta, Narang, & Budhiraja, 2011). Compared to the conventional drug release system the extended-release of the amoxicillin improves the patient's compliance, increases the safety margins, enhances steady drug levels leading to better control of the disease. • The Design of Amoxicillin Sustained the Delivery SystemAmong the delivery systems that are used are the microspheres, which are polymers that are bioadhesive and have micro sizes that can be incorporated into the blood vessels (Arora, Gupta, Narang, & Budhiraja, 2011).
The mucoadhesive microspheres adhere to the mucous membranes of the stomach walls and stay for up to four hours making them the potent carriers for delivering the amoxicillin to kill the H. pylori. The mucoadhesive polymers were made using ethylcellulose as the matrix while the adhesiveness is enhanced by using the carpool 934p (Sevimli, & Yılmaz, 2012).
The recent research studies focus on the improvement of the biodegradable polymers that are used in the delivery system of the amoxicillin drug. Among these are ethylcellulose, beta-cyclodextrins, and chitosan. According to Sevimli and Yılmaz (2012), while establishing the effects of different concentrations of the ethylcellulose on the dissolution profiles of amoxicillin research found out that drug release rates are inversely proportional to the percentage ethylcellulose used as shown in Table 1.1 below.
The release rate of amoxicillin from the formulation that contains equal concentrations of myristic acid and stearic acid gives the most effective sustained release than the formulation containing different combinations of the intestinal fluids, gastric fluids, and either of the acids. From diagram, 1.2 below it is noticeable that there is a sustained-release rate of amoxicillin at 100% when the concentrations of both the myristic (MA) and stearic (SA) acid are equal as compared to the remaining concentrations represented in the figure (Harsha, 2013). The period for the sustained release, in this case, is eight hours, in a 14.5% stearic acid, which can help in achieving a therapeutic concentration (Kumar, 2013).
Matrices in which varying amounts of the carbopol and sodium alginate release the drug in varied ways. • Duration of TherapyDue to the nature of the tablet release, both the pediatrics above 12 years and adults should take 775mg of amoxicillin-sustained release once a day for ten days. To treat active H. pylori infection or a duodenal ulcer of up to a year history, a double therapy of 1g PO q8hr amoxicillin sustained release with lansoprazole 30 mg should be taken for 14 days.
Alternatively, a triple dosage of 1g PO 12hr with lansoprazole30mg and clarithromycin 500mg should be used (Kumar, 2013). • The target areas The dual immediate and sustained release amoxicillin sustained-release tablets bind to the stomach mucosa to provide both the immediate and sustained antibiotic effects on the H. pylori cells. • The site of absorption and the absorption pathway The absorption of the amoxicillin-sustained release occurs due to the presence of the peptides, amino acids, and other beta-lactams in the intestinal walls due to a competitive inhibitory boundary condition.
It is majorly due to the passive absorption that takes place down the concentration gradient on the intestinal surfaces (Kumar, 2013). In striving to correct the intestinal wall concentrations; competitive absorption kinetics takes place thus promotes the absorption of the amoxicillin. Among the factors that affect the drug absorption are the permeability of the beta-lactam, degree of ionization, molecular weight, oil/water partition coefficient of drug and water, and the food drug absorption interactions (Harsha, 2013). Ultraviolet absorption of the tablet is also practical. • Mode of transportWhen taken orally the amoxicillin sustained-release moves along with the GIT by the contraction and relaxation of the tract and then binds to the intestinal walls where it is absorbed.
The sustained release of amoxicillin from its matrix follows the equation: An equation that best describes the rate of the amoxicillin release can be as below: M (t)/M (inf) = kt (n)Where M (t) is the amount of amoxicillin released at a time tM (inf) is the total drug released after a long durationn is an indicative exponent k is a constantConsidering the above equation in an in vitro dissolution of amoxicillin at a pH of 1.2, this is representative of the stomach concentrations (Sevimli, & Yılmaz, 2012).
An increase in the concentrations of the sodium alginate in the Matrices leads to a net in the exponential values of the releasing rates and on the constant k. It is because there increased concentrations of sodium alginate that corrodes and destroys the polymeric matrix thus increases the drug release (Harsha, 2013). Increased carbopol rates, on the other hand, reduce the consistency of the matrix granulation thus offers little resistance to the amoxicillin dissolution increasing its rate of release from the polymer.
The Effect of Ethanol on the rate of formulation release is increasing the release constant values of the equation while and little change on the exponent values. It is attributed to reduced polymer dissolution during granulation thus promotes amoxicillin release rates. In the instances where the matrices were granulated with different amounts of ethanol and water at the same time, the net change in the release profile of amoxicillin was at zero• BioavailabilityThe bioavailability of this sustained release was found to be potent enough despite the fat matrix that led to most of it being excreted in the urine (Arora, Gupta, Narang, & Budhiraja, 2011).
Various studies have however found that ethylcellulose has a slowing effect on the release of Amoxicillin in vitro (Harsha, 2013). The bioavailability of the sustained-release formulation of the amoxicillin is also still lower (30-40) percent as compared to the immediate release capsules, which are fast degraded. The drug carriers, therefore, need enhancements in the matrixes to promote the drug release with higher bioavailability. • Biopharmaceutical barriers When administered orally amoxicillin is easily destroyed by the gastric acid within the stomach.
Its beta-lactam rings are susceptible to hydrolytic degradation at low pH (Sevimli, & Yılmaz, 2012). Increased tableting pressure has also been linked to reduced rates of amoxicillin released from its polymers. The physical barriers to the orally administered sustained-release amoxicillin tablet occur during transcytosis before entering the central lacteals in the intestines due to the first-pass metabolism that occurs (Sevimli, & Yılmaz, 2012).
In some instances, there are immune responses to the matrix that carries the amoxicillin causing antigen-antibody reactions that hinder the effective delivery of the drug. • Research GapsApproving the best polymer to be used in the delivery of amoxicillin is an interest in the research field as identifying the best biodegradable, non-toxic, biocompatible, and mucoadhesive properties for a drug delivery carrier (Harsha, 2013). The differences that affect the drug absorption in different people should be considered to help the poorer absorbers of the drug may also enjoy the drug efficacy. • ConclusionThe sustained release of amoxicillin is developed to maximize the therapeutic concentrations of the drug to enhance its potency against bacterial cells.
The β -lactam rings of the amoxicillin are not degraded when it is coated with sustained-release thus improving its activity of clearing the H. Pylori. They can be orally administered to, and the mucoadhesive polymers used to allow for the sustained release of the drug for a duration that can destroy the bacteria. Numerous factors affect the sustained release rates of the amoxicillin drug. These include the increased compression pressures, which decrease the dissolution rates of the drug and thus its release rates.
Varying percentages of the stearic acids, ethanol, and myristic acid also affect the release rates of the formulation.
Arora, S., Gupta, S., Narang, R. K., & Budhiraja, R. D. (2011). Amoxicillin loaded chitosan–alginate polyelectrolyte complex nanoparticles as mucopenetrating delivery system for H. pylori. Scientia pharmaceutica, 79(3), 673.
Harsha, S. (2013). Pharmaceutical suspension containing both immediate/sustained-release amoxicillin-loaded gelatin nanoparticles: preparation and in vitro characterization. Drug design, development and therapy, 7, 1027.
Kumar, A. (2013). Design and Evaluation of Sustained Release Floating Matrix Tablets of Amoxicillin Trihydrate.
Sevimli, F., & Yılmaz, A. (2012). Surface functionalization of SBA-15 particles for amoxicillin delivery. Microporous and Mesoporous Materials, 158, 281-291.