The oral route of drug administration is the most convenient way of treatment of patients. This convenience has led to the development and availability of tablets and capsules for various ailments, even cancer. Studies show that standard compressed, controlled-release, and coated tablets are the most common form of solid oral dosage. Currently, a wide range and diversity of ingredients are often included in tablet formulations.
According to IQVIA MIDAS Global Data (February 2022), the oral solid dose (OSD) market is $541 billion and has shown steady growth over the past few years. Meanwhile, 72 per cent of newly approved drugs in 2021 were small molecules, and nearly 50 per cent of new drugs approved in 2021 were OSD, as per FDA data.
Moreover, emerging companies hold more than 70 per cent of the total OSD clinical development pipeline and more than 80 per cent of the OSD preclinical development pipeline.
Several industry experts have pointed out that OSD formulations are the pharma industry’s tried-and-true treatment forms. It is not just convenient for the patients, tablets and capsules are efficient and cost-effective to manufacture and shelf stable.
Although billion-dollar large molecule injectable drugs like Humira and Keytruda are topping the market charts, reports suggest small molecule solid dose drugs still make up the vast majority of drugs in the U.S. market.
In recent years, new drug approval for tablets and capsules specifically have outstripped approvals for injectables, solutions, and creams. Additionally, several small molecule OSD products are beginning to show promise in the fight against COVID-19, thrusting aging medications back into the spotlight and renewing patients’ and manufacturers’ enthusiasm for OSD drugs.
What are Oral Solid Dose (OSD) formulations?
The oral solid dosage (OSD) form refers to a final drug product that is ingested through the mouth, dissolved in the digestive system, and delivered to the body through the blood. The most common OSD forms which include tablets and capsules are efficient and cost-effective to manufacture, shelf-stable, and easy to administer. Interestingly, they are widely understood and embraced by patients worldwide. According to experts, they are preferred by pharmaceutical manufacturers owing to the advantage of economy of scale.
“Oral Solid Dose Formulations involve the products like tablets, capsules, sachets, effervescent tablets, sublingual tablets, etc. So, the overall difference between each type of Oral Solid Dose Formulations is mainly dependent upon their nature, their palatability, their strength, their dosage, and their organoleptic parameters,” Dr. Arvind Badiger- technical director at BDR pharma pvt ltd. told Financial Express.com.
Apart from the standard immediate release or sustained release tablets, there are a significant number of oral dosage forms that ensure delivery of active ingredients in the most convenient manner, such as orally disintegrating tablets, timed release capsules etc. in various shapes, sizes, and flavours. It is noteworthy that the wide range and type of available solid dose options makes it possible to respond rapidly and creatively to changing user preferences and market needs as well as the active pharmaceutical ingredients (APIs) properties such as release efficiency, pH-sensitivity, API taste, etc.
There are various forms of OSD: Small molecules, tablets, capsules, soft gels, effervescence, gummies, and pills, and all of them are ingested through the mouth, dissolved in the digestive system, and delivered to the body through absorption into the bloodstream
Originated in 1842 when Englishman William Brockedon patented tablets of compressed sodium and potassium carbonate, OSD formulations are a widely used and well-proven drug delivery system. Today, oral solid dosage drug products are the most common dose form physicians prescribe for a variety of indications.
Why is OSD a dominant mode of medication?
According to industry experts, the oral solid dosage is such a dominant delivery form for three main reasons: easy to administer, well-understood manufacturing methods and well-developed. Interestingly, oral solid dose products continue to lead the charts in novel drug approvals. In 2019, USFDA approved 48 novel drugs and 54 per cent of these drugs were OSD.
In same year, Janssen Pharmaceutical’s Balversa (erdafitinib) tablets were approved under the FDA’s accelerated approval program in April 2019 as a treatment for adult patients with locally advanced or metastatic bladder cancer. Balversa, reportedly the first FGFR kinase inhibitor to receive FDA approval, is an important new therapy for a small subset of patients with urothelial carcinoma who, up until this approval, had limited treatment options.
“With respective effective parameters, Oral Solid Dose Formulations are always considered as patient-friendly dosage forms compared to either injectables or suppositories, topical preparations or inhalations, etc. Once the tablet is consumed by the patient, the patient will get the beneficial effect based on the dosage form. For example, if a person is suffering from acidity, the tablet dosage form or a capsule dosage form if he/ she consumes will give him relief within a certain period of time. However, if the patient consumes the same kind of medicine in the form of apheresis granules like ENO, he can get an effect more in an immediate manner. So, that is how the dosage forms vary with respect to its effectiveness,” Dr Badiger told Financial Express.com.
‘Never-ending demand for Oral Solid Dose Formulation’
According to Vision Research Report, during the forecast period of 2022 to 2030, the global oral solid dosage contract manufacturing market is estimated to develop at a compound annual growth rate (CAGR) of 6.21 per cent. The global oral solid dosage contract manufacturing market was valued at USD 31.93 billion in 2021, and it is predicted to exceed USD 54.9 billion by 2030.
The report also revealed that advances in drug delivery technology, such as the delivery of drugs and sustained release formation, are enabling oral solids to achieve even higher levels of bioavailability while lowering drug administration frequency.
The global market is growing in conjunction with the oncology sector. Clinical-stage cancer programs increased by 77% between 2015 and 2020 (1,642 to 2,911) and completely dominate the landscape, resulting in approximately one-quarter of drugs currently being developed globally being classified as highly potent. Moreover, the COVID-19 crisis has had a number of short- and long-term consequences.
The healthcare sector witnessed a considerable decline in revenue recognition during the year 2020 due to labor shortages and disruption of the raw material supply chain. As small molecule oral solid dosage (OSD) products, such as azithromycin and hydroxychloroquine have a positive impact on the COVID-19-infected population, there is an increasing number of manufacturers were focused on the commercialisation and production of such OSD drug products, and supporting the market growth.
Moreover, the industry witnessed a significant surge in 2020 and 2021, as a new and high number of CMOs were allocated with contracts of OSD as a potential treatment of the COVID-19 infection. In August 2020, Pfizer Inc. announced an agreement with Gilead Sciences, Inc. to provide contract manufacturing services for the supply and manufacturing of Gilead’s investigational antiviral remdesivir drug, with an aim to scale up the supply of the investigational treatment for COVID-19 patients. These factors supported the demand surge of OSD products across 2020 and 2021.
’90 per cent of Cancer Medication is in Oral Solid Dosage form’
According to the Market Watch 2022 report, the tablets segment dominated the OSD contract manufacturing market last year. The report also revealed that it accounted for the largest share of 32.7 per cent of the global revenue. Several studies have highlighted that the clinical-stage cancer programmes increased by 77 per cent between 2015 and 2020 (1,642 to 2,911) and completely dominate the landscape, resulting in approximately one-quarter of drugs currently being developed globally being classified as highly potent.
“The involvement of OSD or the contribution of OSD in cancer treatment has been quite phenomenal because many of the drugs which are used for cancer treatment are quite toxic in nature. Therefore, injectable anti-cancer drugs are comparatively less when you see the total number of molecules,” Dr. Badiger told Financial Express.com.
He also highlighted that 90 per cent of the products which are available in the treatment of cancer are available in the form of oral solid dosage forms and the rest of the 10 per cent are available in injectable dosage forms.
“Oral solid dosage forms have been contributing majorly to the treatment of anti-cancer drugs and if we look at the future pipeline of production, it is also concentrated mainly on the oral solid dosage form. However, this is specifically mentioned in chemotherapy or immunomodulating drugs. But when we look at the monoclonal antibodies or biosimilar kinds of products there we have a good number of products that are available in injectable forms as well,” he added.
Oral Solid dosages in India’s cancer care segment
In India, according to a 2018 study in the Indian Journal of Medical Research, almost 75-80 per cent of patients have advanced disease (Stage 3-4) at the time of diagnosis. The treatment of this deadly disease is limited by the affordability of patients in countries like India. Currently, cancer patients receive a combination of treatments, including surgery, chemotherapy, radiation therapy, and immunotherapy.
Earlier this month, four major anti-cancer drugs were added to the National List of Essential Medicines (NLEM).
The Union health ministry released the NLEM 2022 list with 34 additions, including the cancer drugs Bendamustine Hydrochloride, HCI Trihydrate, Lenalidomide and Leuprolide Acetate, taking the number of medicines on the list to 384 across 27 categories. According to the central government, this move will help in reducing “patients’ out-of-pocket expenditure”.
Four major anti-cancer drugs – Bendamustine Hydrochloride, Irinotecan HCI Trihydrate, Lenalidomide, and Leuprolide acetate which is effective in various types of cancers have been added to the list.
Dr. Badiger told Financial Express.com that various factors are driving the growth in OSD manufacturing now that automation has become phenomenally significant.
“Now the manufacturing is done under the isolator technology, thereby the psychotoxic property of the medicine is not affecting the operators. More importantly, the trace and tracks have evolved in order to understand the entire manufacturing process of the solid dosage form in order to trace it to the basics. The technology has been further significantly changed after the granulation has developed,” he said.
Dr. Badiger also said that earlier the tables were manufactured with equipment like rapid mixer granulators, now there are high shear granulators, top spray regulators, single port regulators, automatic exclusion regulators etc. “where the evolution has helped the assumed management of anti-cancer products.”
“Efficacy varies from molecule to molecule and it depends upon the type of cancer that the property is going to treat. So it definitely varies from molecule to molecule and also it depends largely upon the kind of treatment you are targeting it to,” he added.
OSD formulations: A Patient-Centric Alternative for Cancer Treatment
Dr. Badiger also explained that most chemotherapeutic anticancer drugs are available in the oral solid dosage form.
“Most of the OSDs that are available in the current scenario are tablet dosage form largely. Some of them are present in soft gelatin capsules some of the are present in hard gelatin capsules and hardly a few are present in suspension dosage form and solution dosage form. One of the challenges for the anti-cancer product is that the product needs to be protected to be exposed to the environment as they are psychotoxic in nature, particularly to the paramedical staff or caretaker of the patient,” he added.
Moreover, OSDs are not divided as per the type of cancer. Rather, it is the type of molecules that are divided based on the type of cancer.
“…For example, we have various immunomodulators like everolimus which are used for breast cancer treatment and they are available in tablet dosage form. Whereas there is a product like enzalutamide which is present in the soft gelatin capsule that will be used for the treatment of prostate cancer. In the same way, there is a product like abiraterone which is present in the form of a tablet and is used for the treatment of prostate cancer. The same formulation of enzalutamide which is available in the form of soft gelatin capsule is now converted into a tablet dosage form and both of them are being used internationally for the treatment of prostate cancer. So, the type of OSDs will not determine the treatment of type of cancers rather the type of molecules will determine the treatment of the different types of cancer,” He said.
Meanwhile, there are various types of products already available in the market.
“We have a product like Cyclophosphamide that is a very old conventional tablet dosage form which is a highly psychotoxic drug used in the treatment of cancer. There is a product like capecitabine that is also highly toxic in nature and it is used in the treatment of various types of cancer such as androgen receptor inhibitor which is used in the treatment of cancer. So, it is the type of molecules that make the difference in the treatment of different cancer, it is not the types of dosage forms,” Dr. Badiger said.
He also informed that efficacy varies from molecule to molecule and it depends upon the type of cancer that the property is going to treat. “So it definitely varies from molecule to molecule and also it depends largely upon the kind of treatment you are targeting it to,” Dr. Badiger said.
‘Tablets dominate OSD contract manufacturing market’
According to the Market Watch 2022 report, the tablets segment dominated the OSD contract manufacturing market in 2021 and accounted for the largest share of 32.7 percent of the global revenue. Tablets are the most common OSD form.
Tablets contain an Active Pharmaceutical Ingredient (API), which is also known as a dry powder ingredient and a drug substance. According to experts, the method of compression is used to form tablets, which can be coated or uncoated.
Experts have revealed that pharmaceutical companies have a preference for tablets as they are simple to make, package, and transport, have good physical and chemical stability, and allow for simple and accurate dosing.
Moreover, the capsules segment is expected to register the fastest CAGR over the forecast period and is the second-most lucrative dosage form in the market. It is noteworthy that capsules are a widely known oral dosage formulation that is common among both pharmaceutical companies and consumers.
Asia Pacific is projected to be the fastest-growing regional market with a CAGR of 6.4 percent over the forecast period. The region also accounted for the largest market share in 2021. India and China are OSD CMO market powerhouses in the APAC region, with significantly lower prices, the report revealed.
According to the report, one area of the OSD market in particular expected to expand is the development and manufacturing of highly potent active pharmaceutical ingredients (HPAPIs).