**5. Various new dosage forms, making their way to the market**

#### **5.1. Research in the development of new delivery system with existing analgesic**

Development of modified release painkiller is a popular research. This type of research looks into the development of techniques and evaluation of the modified forms used in the man‐ agement of chronic pain in comparison with existing dosage form [7]. The realization on the importance of pain management and the treatment of pain has initiated more research in this area among healthcare researchers. Modified‐release products have enabled patients to better maintain pain control due to convenient dosing intervals and sustained blood concentrations. With the above statements, it is evidenced that development of modified release is very much needed for pain management drug, so as to be very effective and to prolong the effect for more effective pain management [7].

All drugs need a delivery system to deliver it to the site of action upon administration. Delivery of the drugs can be achieved using various types of dosage forms including tablets, capsules, creams, ointments, liquids, aerosols, injections, and suppositories. These conventional drug delivery systems provide immediate release of the drug without controlling the rate or drug release. A number of doses given daily in order to achieve and maintain therapeutic level to achieve effective plasma concentrations cause fluctuations in plasma levels of the drug [8–10] and drug plasma levels could fall below the minimum effective concentration and can also exceed the minimum toxic concentration (**Figure 1**).

## **5.2. The various types of modified release preparation possible for analgesics delivery**

The purpose behind controlling the drug delivery for analgesic are to achieve more effective therapies while eliminating the potential for both under‐ and overdosing of analgesic.

Maintenance of analgesic levels within a desired range to combat pain is indirectly combat‐ ing stress to the patient. The need for fewer administrations of analgesic or optimal use of

**Figure 1.** The conventional four times daily oral doses of diclofenac sodium (25 mg) plasma level compared to a daily doses sustained release formulation (100 mg) plasma level.

analgesic toward "no pain" maintenance is to avoid adverse side effect and indirectly to increase patient compliance in their pain management [8].

#### *5.2.1. The polymeric delivery system: polymers in controlled drug delivery*

The use of various polymers in controlled drug delivery is very popular among formula‐ tion researchers. These polymers can be natural or synthetic in nature. Different polymer is combined with a drug in such a way that the active agent is released from the material in a predesigned manner. The release of the active agent may be constant over a long period or it may be cyclic over a long period or it may be triggered by the environment or other external events [9].

Polymer can be used to encapsulate drug molecules for the purpose of sustaining the release and extending the availability of the drug so that dosage administration frequency can be reduced while maintaining the plasma level steady state. A good example would be the sus‐ tenance of release preparation of diclofenac sodium for oral administration [8].

Polymer can also be used in protecting the drug from the environment in order to target the delivery of the drug to certain side of the body. A very simple targeting is the delivery of weak base drug to the small intestine where most of this type of drug is acid labile. So the polymer is used as a protective shield. This can be a pH‐sensitive polymer where in acidic environment it is very stable and will disintegrate in basic environment.

Characteristics of polymer may be engineered to the advantage in the development of a drug delivery system. A mucoadhesive polymer which can stick to the mucosa can be used to encap‐ sulate drug and attach to the mucosa and sustain the release of the drug it encapsulates. A biode‐ gradable polymer can be used to encapsulate drug for slow release as the polymer degrades. A pH‐sensitive polymer can be used to target the release of drug either in acidic or basic environ‐ ment. Combining all these characteristic, a researcher can even deliver a drug which currently can only be delivered by parenteral route, using the enthrall route. Logically, the drug can have an outer encapsulation with a pH‐sensitive polymer which can save it from the acidic environ‐ ment in the stomach and can have a mucoadhesive polymer inner encapsulation for it to stick to the small intestine lining and to release the drug direct across the membrane into the blood.

The vast uses of polymer in the gastrointestinal, enthrall, or oral drug delivery system do not limit the same polymer to be used in other route of dosage administration. Several polymers in the form of nano size particles are used to deliver drug as an intravenous dosage form [11]. Researchers are also looking into various polymers which can act as a depot for big dose administration of drug through implantation in the subcutaneous area for cases of difficult patient compliance such as delivery of antipsychotics and cancer drugs.

Some of the synthetic materials that are currently being used or studied for controlled drug delivery are as depicted in **Table 2**.

Polymer are sometimes crudely extracted from natural resources be it from animals or from plants. Such natural materials are depicted in **Table 3**.

analgesic toward "no pain" maintenance is to avoid adverse side effect and indirectly to

**Figure 1.** The conventional four times daily oral doses of diclofenac sodium (25 mg) plasma level compared to a daily

The use of various polymers in controlled drug delivery is very popular among formula‐ tion researchers. These polymers can be natural or synthetic in nature. Different polymer is combined with a drug in such a way that the active agent is released from the material in a predesigned manner. The release of the active agent may be constant over a long period or it may be cyclic over a long period or it may be triggered by the environment or other external

Polymer can be used to encapsulate drug molecules for the purpose of sustaining the release and extending the availability of the drug so that dosage administration frequency can be reduced while maintaining the plasma level steady state. A good example would be the sus‐

Polymer can also be used in protecting the drug from the environment in order to target the delivery of the drug to certain side of the body. A very simple targeting is the delivery of weak base drug to the small intestine where most of this type of drug is acid labile. So the polymer is used as a protective shield. This can be a pH‐sensitive polymer where in acidic environment

Characteristics of polymer may be engineered to the advantage in the development of a drug delivery system. A mucoadhesive polymer which can stick to the mucosa can be used to encap‐ sulate drug and attach to the mucosa and sustain the release of the drug it encapsulates. A biode‐ gradable polymer can be used to encapsulate drug for slow release as the polymer degrades. A pH‐sensitive polymer can be used to target the release of drug either in acidic or basic environ‐ ment. Combining all these characteristic, a researcher can even deliver a drug which currently can only be delivered by parenteral route, using the enthrall route. Logically, the drug can have an outer encapsulation with a pH‐sensitive polymer which can save it from the acidic environ‐ ment in the stomach and can have a mucoadhesive polymer inner encapsulation for it to stick to the small intestine lining and to release the drug direct across the membrane into the blood.

tenance of release preparation of diclofenac sodium for oral administration [8].

increase patient compliance in their pain management [8].

doses sustained release formulation (100 mg) plasma level.

16 Pain Relief - From Analgesics to Alternative Therapies

it is very stable and will disintegrate in basic environment.

events [9].

*5.2.1. The polymeric delivery system: polymers in controlled drug delivery*

**Table 2.** Example of synthetic polymer available in the market.

#### **5.3. Controlled‐release mechanisms in the case of using polymer as a drug delivery system**

There are three primary mechanisms by which active agents can be released from a delivery system: diffusion, degradation, and swelling followed by diffusion. Any or all of these mechanisms may occur in a given release system [12]. We can easily understand this mechanism through **Figures 2**–**8**.


**Table 3.** Example of natural polymer used in drug delivery research.

**5.3. Controlled‐release mechanisms in the case of using polymer as a drug delivery system**

**Polymer Polymer structure**

18 Pain Relief - From Analgesics to Alternative Therapies

Poly(vinyl alcohol).

Poly(acrylic acid).

Polyacrylamide.

Poly(ethylene‐co‐vinyl acetate).

Poly(ethylene glycol). **C**2n**H**4n+2**O**n+1

Poly(methacrylic acid).

**(C**<sup>2</sup> **H**4 **O)x**

**(C**<sup>3</sup> **H**4 **O**2 **)**n

**(C**<sup>3</sup> **H**5 **NO)**<sup>n</sup>

**(C**<sup>2</sup> **H**4 **)**n**(C**<sup>4</sup> **H**6 **O**2 **)**m

**(C**<sup>4</sup> **H**6 **O**2 **)**n

There are three primary mechanisms by which active agents can be released from a delivery system: diffusion, degradation, and swelling followed by diffusion. Any or all of these mechanisms may occur in a given release system [12]. We can easily understand this

mechanism through **Figures 2**–**8**.

**Table 2.** Example of synthetic polymer available in the market.

**Figure 2.** Analgesic diffusing out from a matrix of polymer in a sustain release model.

**Figure 3.** A dermal patch model illustrating the diffusion analgesic from a dermal path polymer matrix.

**Figure 4.** Analgesic delivery system by swelling of polymer acting as drug reservoir.

**Figure 5.** Analgesic delivery system by swelling of the polymer matrix encapsulating the drug.

Advance Delivery System Dosage Form for Analgesic, Their Rationale, and Specialty http://dx.doi.org/10.5772/68096 21

**Figure 6.** Drug delivery from environmental sensitive release system.

**Figure 2.** Analgesic diffusing out from a matrix of polymer in a sustain release model.

20 Pain Relief - From Analgesics to Alternative Therapies

**Figure 4.** Analgesic delivery system by swelling of polymer acting as drug reservoir.

**Figure 5.** Analgesic delivery system by swelling of the polymer matrix encapsulating the drug.

**Figure 3.** A dermal patch model illustrating the diffusion analgesic from a dermal path polymer matrix.

**Figure 7.** Bulk eroding biodegradable polymeric delivery system.

**Figure 8.** Surface eroding biodegradable polymeric delivery system.
